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2019


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.

pf

[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 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 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.

pf

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]


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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]


Thumb xl as20205.f2
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)

pi

[BibTex]

[BibTex]


Thumb xl woodw1 2892811 large
Tailored Magnetic Springs for Shape-Memory Alloy Actuated Mechanisms in Miniature Robots

Woodward, M. A., Sitti, M.

IEEE Transactions on Robotics, 35, 2019 (article)

Abstract
Animals can incorporate large numbers of actuators because of the characteristics of muscles; whereas, robots cannot, as typical motors tend to be large, heavy, and inefficient. However, shape-memory alloys (SMA), materials that contract during heating because of change in their crystal structure, provide another option. SMA, though, is unidirectional and therefore requires an additional force to reset (extend) the actuator, which is typically provided by springs or antagonistic actuation. These strategies, however, tend to limit the actuator's work output and functionality as their force-displacement relationships typically produce increasing resistive force with limited variability. In contrast, magnetic springs-composed of permanent magnets, where the interaction force between magnets mimics a spring force-have much more variable force-displacement relationships and scale well with SMA. However, as of yet, no method for designing magnetic springs for SMA-actuators has been demonstrated. Therefore, in this paper, we present a new methodology to tailor magnetic springs to the characteristics of these actuators, with experimental results both for the device and robot-integrated SMA-actuators. We found magnetic building blocks, based on sets of permanent magnets, which are well-suited to SMAs and have the potential to incorporate features such as holding force, state transitioning, friction minimization, auto-alignment, and self-mounting. We show magnetic springs that vary by more than 3 N in 750 $\mu$m and two SMA-actuated devices that allow the MultiMo-Bat to reach heights of up to 4.5 m without, and 3.6 m with, integrated gliding airfoils. Our results demonstrate the potential of this methodology to add previously impossible functionality to smart material actuators. We anticipate this methodology will inspire broader consideration of the use of magnetic springs in miniature robots and further study of the potential of tailored magnetic springs throughout mechanical systems.

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DOI [BibTex]


Thumb xl c8sm02215a f1 hi res
The near and far of a pair of magnetic capillary disks

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

Soft Matter, 2019 (article)

pi

[BibTex]

[BibTex]


Thumb xl smll201900472 fig 0001 m
Multifarious Transit Gates for Programmable Delivery of Bio‐functionalized Matters

Hu, X., Torati, S. R., Kim, H., Yoon, J., Lim, B., Kim, K., Sitti, M., Kim, C.

Small, Wiley Online Library, 2019 (article)

pi

[BibTex]

[BibTex]


Thumb xl smll201900472 fig 0001 m
Mechanics of a pressure-controlled adhesive membrane for soft robotic gripping on curved surfaces

Song, S., Drotlef, D., Paik, J., Majidi, C., Sitti, M.

Extreme Mechanics Letters, Elsevier, 2019 (article)

pi

[BibTex]


Thumb xl mt 2018 00757w 0007
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)

pi

[BibTex]

[BibTex]


Thumb xl itxm a 1566425 f0001 c
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)

pi

[BibTex]

[BibTex]


Thumb xl adtp201800064 fig 0004 m
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)

pi

[BibTex]

[BibTex]


Thumb xl adom201801313 fig 0001 m
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)

pi

[BibTex]

[BibTex]


Thumb xl 201904010817153241
ENGINEERING Bio-inspired robotic collectives

Sitti, M.

Nature, 567, pages: 314-315, Macmillan Publishers Ltd., London, England, 2019 (article)

pi

[BibTex]

[BibTex]


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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]

2017


Thumb xl hines et al 2016 advanced materials
Soft Actuators for Small-Scale Robotics

Hines, L., Petersen, K., Lum, G. Z., Sitti, M.

Advanced Materials, 2017 (article)

Abstract
This review comprises a detailed survey of ongoing methodologies for soft actuators, highlighting approaches suitable for nanometer- to centimeter-scale robotic applications. Soft robots present a special design challenge in that their actuation and sensing mechanisms are often highly integrated with the robot body and overall functionality. When less than a centimeter, they belong to an even more special subcategory of robots or devices, in that they often lack on-board power, sensing, computation, and control. Soft, active materials are particularly well suited for this task, with a wide range of stimulants and a number of impressive examples, demonstrating large deformations, high motion complexities, and varied multifunctionality. Recent research includes both the development of new materials and composites, as well as novel implementations leveraging the unique properties of soft materials.

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DOI [BibTex]


Thumb xl fig1
Active colloidal propulsion over a crystalline surface

Choudhury, U., Straube, A., Fischer, P., Gibbs, J., Höfling, F.

New Journal of Physics, 19, pages: 125010, December 2017 (article)

Abstract
We study both experimentally and theoretically the dynamics of chemically self-propelled Janus colloids moving atop a two-dimensional crystalline surface. The surface is a hexagonally close-packed monolayer of colloidal particles of the same size as the mobile one. The dynamics of the self-propelled colloid reflects the competition between hindered diffusion due to the periodic surface and enhanced diffusion due to active motion. Which contribution dominates depends on the propulsion strength, which can be systematically tuned by changing the concentration of a chemical fuel. The mean-square displacements obtained from the experiment exhibit enhanced diffusion at long lag times. Our experimental data are consistent with a Langevin model for the effectively two-dimensional translational motion of an active Brownian particle in a periodic potential, combining the confining effects of gravity and the crystalline surface with the free rotational diffusion of the colloid. Approximate analytical predictions are made for the mean-square displacement describing the crossover from free Brownian motion at short times to active diffusion at long times. The results are in semi-quantitative agreement with numerical results of a refined Langevin model that treats translational and rotational degrees of freedom on the same footing.

pf

link (url) DOI [BibTex]

link (url) DOI [BibTex]


Thumb xl 41315 2017 39 fig3 html
A deep learning based fusion of RGB camera information and magnetic localization information for endoscopic capsule robots

Turan, M., Shabbir, J., Araujo, H., Konukoglu, E., Sitti, M.

International Journal of Intelligent Robotics and Applications, 1(4):442-450, December 2017 (article)

Abstract
A reliable, real time localization functionality is crutial for actively controlled capsule endoscopy robots, which are an emerging, minimally invasive diagnostic and therapeutic technology for the gastrointestinal (GI) tract. In this study, we extend the success of deep learning approaches from various research fields to the problem of sensor fusion for endoscopic capsule robots. We propose a multi-sensor fusion based localization approach which combines endoscopic camera information and magnetic sensor based localization information. The results performed on real pig stomach dataset show that our method achieves sub-millimeter precision for both translational and rotational movements.

pi

link (url) DOI [BibTex]

link (url) DOI [BibTex]


Thumb xl 3d mikroroboterb
3D Chemical Patterning of Micromaterials for Encoded Functionality

Ceylan, H., Yasa, I. C., Sitti, M.

Advanced Materials, 2017 (article)

Abstract
Programming local chemical properties of microscale soft materials with 3D complex shapes is indispensable for creating sophisticated functionalities, which has not yet been possible with existing methods. Precise spatiotemporal control of two-photon crosslinking is employed as an enabling tool for 3D patterning of microprinted structures for encoding versatile chemical moieties.

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DOI Project Page [BibTex]


Thumb xl f2.large
Biohybrid actuators for robotics: A review of devices actuated by living cells

Ricotti, L., Trimmer, B., Feinberg, A. W., Raman, R., Parker, K. K., Bashir, R., Sitti, M., Martel, S., Dario, P., Menciassi, A.

Science Robotics, 2(12), Science Robotics, November 2017 (article)

Abstract
Actuation is essential for artificial machines to interact with their surrounding environment and to accomplish the functions for which they are designed. Over the past few decades, there has been considerable progress in developing new actuation technologies. However, controlled motion still represents a considerable bottleneck for many applications and hampers the development of advanced robots, especially at small length scales. Nature has solved this problem using molecular motors that, through living cells, are assembled into multiscale ensembles with integrated control systems. These systems can scale force production from piconewtons up to kilonewtons. By leveraging the performance of living cells and tissues and directly interfacing them with artificial components, it should be possible to exploit the intricacy and metabolic efficiency of biological actuation within artificial machines. We provide a survey of important advances in this biohybrid actuation paradigm.

pi

link (url) DOI [BibTex]

link (url) DOI [BibTex]


Thumb xl fig1
Wireless Acoustic-Surface Actuators for Miniaturized Endoscopes

Qiu, T., Adams, F., Palagi, S., Melde, K., Mark, A. G., Wetterauer, U., Miernik, A., Fischer, P.

ACS Applied Materials & Interfaces, 9(49):42536 - 42543, November 2017 (article)

Abstract
Endoscopy enables minimally invasive procedures in many medical fields, such as urology. However, current endoscopes are normally cable-driven, which limits their dexterity and makes them hard to miniaturize. Indeed current urological endoscopes have an outer diameter of about 3 mm and still only possess one bending degree of freedom. In this paper, we report a novel wireless actuation mechanism that increases the dexterity and that permits the miniaturization of a urological endoscope. The novel actuator consists of thin active surfaces that can be readily attached to any device and are wirelessly powered by ultrasound. The surfaces consist of two-dimensional arrays of micro-bubbles, which oscillate under ultrasound excitation and thereby generate an acoustic streaming force. Bubbles of different sizes are addressed by their unique resonance frequency, thus multiple degrees of freedom can readily be incorporated. Two active miniaturized devices (with a side length of around 1 mm) are demonstrated: a miniaturized mechanical arm that realizes two degrees of freedom, and a flexible endoscope prototype equipped with a camera at the tip. With the flexible endoscope, an active endoscopic examination is successfully performed in a rabbit bladder. This results show the potential medical applicability of surface actuators wirelessly powered by ultrasound penetrating through biological tissues.

pf

link (url) DOI Project Page [BibTex]

link (url) DOI Project Page [BibTex]


Thumb xl 7 byung fig
Multifunctional Bacteria-Driven Microswimmers for Targeted Active Drug Delivery

Park, B., Zhuang, J., Yasa, O., Sitti, M.

ACS Nano, 11(9):8910-8923, September 2017, PMID: 28873304 (article)

Abstract
High-performance, multifunctional bacteria-driven microswimmers are introduced using an optimized design and fabrication method for targeted drug delivery applications. These microswimmers are made of mostly single Escherichia coli bacterium attached to the surface of drug-loaded polyelectrolyte multilayer (PEM) microparticles with embedded magnetic nanoparticles. The PEM drug carriers are 1 μm in diameter and are intentionally fabricated with a more viscoelastic material than the particles previously studied in the literature. The resulting stochastic microswimmers are able to swim at mean speeds of up to 22.5 μm/s. They can be guided and targeted to specific cells, because they exhibit biased and directional motion under a chemoattractant gradient and a magnetic field, respectively. Moreover, we demonstrate the microswimmers delivering doxorubicin anticancer drug molecules, encapsulated in the polyelectrolyte multilayers, to 4T1 breast cancer cells under magnetic guidance in vitro. The results reveal the feasibility of using these active multifunctional bacteria-driven microswimmers to perform targeted drug delivery with significantly enhanced drug transfer, when compared with the passive PEM microparticles.

pi

link (url) DOI Project Page [BibTex]


Thumb xl admi201770108 gra 0001 m
Active Acoustic Surfaces Enable the Propulsion of a Wireless Robot

Qiu, T., Palagi, S., Mark, A. G., Melde, K., Adams, F., Fischer, P.

Advanced Materials Interfaces, 4(21):1700933, September 2017 (article)

Abstract
A major challenge that prevents the miniaturization of mechanically actuated systems is the lack of suitable methods that permit the efficient transfer of power to small scales. Acoustic energy holds great potential, as it is wireless, penetrates deep into biological tissues, and the mechanical vibrations can be directly converted into directional forces. Recently, active acoustic surfaces are developed that consist of 2D arrays of microcavities holding microbubbles that can be excited with an external acoustic field. At resonance, the surfaces give rise to acoustic streaming and thus provide a highly directional propulsive force. Here, this study advances these wireless surface actuators by studying their force output as the size of the bubble-array is increased. In particular, a general method is reported to dramatically improve the propulsive force, demonstrating that the surface actuators are actually able to propel centimeter-scale devices. To prove the flexibility of the functional surfaces as wireless ready-to-attach actuator, a mobile mini-robot capable of propulsion in water along multiple directions is presented. This work paves the way toward effectively exploiting acoustic surfaces as a novel wireless actuation scheme at small scales.

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link (url) DOI Project Page [BibTex]


Thumb xl publications toc
EndoSensorFusion: Particle Filtering-Based Multi-sensory Data Fusion with Switching State-Space Model for Endoscopic Capsule Robots

Turan, M., Almalioglu, Y., Gilbert, H., Araujo, H., Cemgil, T., Sitti, M.

ArXiv e-prints, September 2017 (article)

Abstract
A reliable, real time multi-sensor fusion functionality is crucial for localization of actively controlled capsule endoscopy robots, which are an emerging, minimally invasive diagnostic and therapeutic technology for the gastrointestinal (GI) tract. In this study, we propose a novel multi-sensor fusion approach based on a particle filter that incorporates an online estimation of sensor reliability and a non-linear kinematic model learned by a recurrent neural network. Our method sequentially estimates the true robot pose from noisy pose observations delivered by multiple sensors. We experimentally test the method using 5 degree-of-freedom (5-DoF) absolute pose measurement by a magnetic localization system and a 6-DoF relative pose measurement by visual odometry. In addition, the proposed method is capable of detecting and handling sensor failures by ignoring corrupted data, providing the robustness expected of a medical device. Detailed analyses and evaluations are presented using ex-vivo experiments on a porcine stomach model prove that our system achieves high translational and rotational accuracies for different types of endoscopic capsule robot trajectories.

pi

link (url) Project Page [BibTex]


Thumb xl publications toc
Endo-VMFuseNet: Deep Visual-Magnetic Sensor Fusion Approach for Uncalibrated, Unsynchronized and Asymmetric Endoscopic Capsule Robot Localization Data

Turan, M., Almalioglu, Y., Gilbert, H., Eren Sari, A., Soylu, U., Sitti, M.

ArXiv e-prints, September 2017 (article)

Abstract
In the last decade, researchers and medical device companies have made major advances towards transforming passive capsule endoscopes into active medical robots. One of the major challenges is to endow capsule robots with accurate perception of the environment inside the human body, which will provide necessary information and enable improved medical procedures. We extend the success of deep learning approaches from various research fields to the problem of uncalibrated, asynchronous, and asymmetric sensor fusion for endoscopic capsule robots. The results performed on real pig stomach datasets show that our method achieves sub-millimeter precision for both translational and rotational movements and contains various advantages over traditional sensor fusion techniques.

pi

link (url) Project Page [BibTex]


Thumb xl comp 5d copy
Magnetotactic Bacteria Powered Biohybrids Target E. coli Biofilms

Stanton, M. M., Park, B., Vilela, D., Bente, K., Faivre, D., Sitti, M., Sánchez, S.

ACS Nano, 0(0):null, September 2017, PMID: 28933815 (article)

Abstract
Biofilm colonies are typically resistant to general antibiotic treatment and require targeted methods for their removal. One of these methods includes the use of nanoparticles as carriers for antibiotic delivery, where they randomly circulate in fluid until they make contact with the infected areas. However, the required proximity of the particles to the biofilm results in only moderate efficacy. We demonstrate here that the nonpathogenic magnetotactic bacteria Magnetosopirrillum gryphiswalense (MSR-1) can be integrated with drug-loaded mesoporous silica microtubes to build controllable microswimmers (biohybrids) capable of antibiotic delivery to target an infectious biofilm. Applying external magnetic guidance capability and swimming power of the MSR-1 cells, the biohybrids are directed to and forcefully pushed into matured Escherichia coli (E. coli) biofilms. Release of the antibiotic, ciprofloxacin, is triggered by the acidic microenvironment of the biofilm, ensuring an efficient drug delivery system. The results reveal the capabilities of a nonpathogenic bacteria species to target and dismantle harmful biofilms, indicating biohybrid systems have great potential for antibiofilm applications.

pi

link (url) DOI Project Page [BibTex]

link (url) DOI Project Page [BibTex]


Thumb xl jeong et al 2017 advanced science
Corrosion-Protected Hybrid Nanoparticles

Jeong, H. H., Alarcon-Correa, M., Mark, A. G., Son, K., Lee, T., Fischer, P.

Advanced Science, 4(12):1700234, September 2017 (article)

Abstract
Nanoparticles composed of functional materials hold great promise for applications due to their unique electronic, optical, magnetic, and catalytic properties. However, a number of functional materials are not only difficult to fabricate at the nanoscale, but are also chemically unstable in solution. Hence, protecting nanoparticles from corrosion is a major challenge for those applications that require stability in aqueous solutions and biological fluids. Here, this study presents a generic scheme to grow hybrid 3D nanoparticles that are completely encapsulated by a nm thick protective shell. The method consists of vacuum-based growth and protection, and combines oblique physical vapor deposition with atomic layer deposition. It provides wide flexibility in the shape and composition of the nanoparticles, and the environments against which particles are protected. The work demonstrates the approach with multifunctional nanoparticles possessing ferromagnetic, plasmonic, and chiral properties. The present scheme allows nanocolloids, which immediately corrode without protection, to remain functional, at least for a week, in acidic solutions.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Sparse-then-Dense Alignment based 3D Map Reconstruction Method for Endoscopic Capsule Robots

Turan, M., Yigit Pilavci, Y., Ganiyusufoglu, I., Araujo, H., Konukoglu, E., Sitti, M.

ArXiv e-prints, August 2017 (article)

Abstract
Since the development of capsule endoscopcy technology, substantial progress were made in converting passive capsule endoscopes to robotic active capsule endoscopes which can be controlled by the doctor. However, robotic capsule endoscopy still has some challenges. In particular, the use of such devices to generate a precise and globally consistent three-dimensional (3D) map of the entire inner organ remains an unsolved problem. Such global 3D maps of inner organs would help doctors to detect the location and size of diseased areas more accurately, precisely, and intuitively, thus permitting more accurate and intuitive diagnoses. The proposed 3D reconstruction system is built in a modular fashion including preprocessing, frame stitching, and shading-based 3D reconstruction modules. We propose an efficient scheme to automatically select the key frames out of the huge quantity of raw endoscopic images. Together with a bundle fusion approach that aligns all the selected key frames jointly in a globally consistent way, a significant improvement of the mosaic and 3D map accuracy was reached. To the best of our knowledge, this framework is the first complete pipeline for an endoscopic capsule robot based 3D map reconstruction containing all of the necessary steps for a reliable and accurate endoscopic 3D map. For the qualitative evaluations, a real pig stomach is employed. Moreover, for the first time in literature, a detailed and comprehensive quantitative analysis of each proposed pipeline modules is performed using a non-rigid esophagus gastro duodenoscopy simulator, four different endoscopic cameras, a magnetically activated soft capsule robot (MASCE), a sub-millimeter precise optical motion tracker and a fine-scale 3D optical scanner.

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link (url) Project Page [BibTex]

link (url) Project Page [BibTex]


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Dipole codes attractively encode glue functions

Ipparthi, D., Mastrangeli, M., Winslow, A.

Theoretical Computer Science, 671, pages: 19 - 25, August 2017, Computational Self-Assembly (article)

Abstract
Dipole words are sequences of magnetic dipoles, in which alike elements repel and opposite elements attract. Magnetic dipoles contrast with more general sets of bonding types, called glues, in which pairwise bonding strength is specified by a glue function. We prove that every glue function g has a set of dipole words, called a dipole code, that attractively encodes g: the pairwise attractions (positive or non-positive bond strength) between the words are identical to those of g. Moreover, we give such word sets of asymptotically optimal length. Similar results are obtained for a commonly used subclass of glue functions.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Hypoxia‐enhanced adhesion of red blood cells in microscale flow

Kim, M., Alapan, Y., Adhikari, A., Little, J. A., Gurkan, U. A.

Microcirculation, 24(5):e12374, July 2017 (article)

Abstract
Abstract Objectives The advancement of microfluidic technology has facilitated the simulation of physiological conditions of the microcirculation, such as oxygen tension, fluid flow, and shear stress in these devices. Here, we present a micro‐gas exchanger integrated with microfluidics to study RBC adhesion under hypoxic flow conditions mimicking postcapillary venules. Methods We simulated a range of physiological conditions and explored RBC adhesion to endothelial or subendothelial components (FN or LN). Blood samples were injected into microchannels at normoxic or hypoxic physiological flow conditions. Quantitative evaluation of RBC adhesion was performed on 35 subjects with homozygous SCD. Results Significant heterogeneity in RBC adherence response to hypoxia was seen among SCD patients. RBCs from a HEA population showed a significantly greater increase in adhesion compared to RBCs from a HNA population, for both FN and LN. Conclusions The approach presented here enabled the control of oxygen tension in blood during microscale flow and the quantification of RBC adhesion in a cost‐efficient and patient‐specific manner. We identified a unique patient population in which RBCs showed enhanced adhesion in hypoxia in vitro. Clinical correlates suggest a more severe clinical phenotype in this subgroup.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Soiled adhesive pads shear clean by slipping: a robust self-cleaning mechanism in climbing beetles

Amador, G., Endlein, T., Sitti, M.

Journal of The Royal Society Interface, 14(131):20170134, The Royal Society, June 2017 (article)

Abstract
Animals using adhesive pads to climb smooth surfaces face the problem of keeping their pads clean and functional. Here, a self-cleaning mechanism is proposed whereby soiled feet would slip on the surface due to a lack of adhesion but shed particles in return. Our study offers an in situ quantification of self-cleaning performance in fibrillar adhesives, using the dock beetle as a model organism. After beetles soiled their pads by stepping into patches of spherical beads, we found that their gait was significantly affected. Specifically, soiled pads slipped 10 times further than clean pads, with more particles deposited for longer slips. Like previous studies, we found that particle size affected cleaning performance. Large (45 μm) beads were removed most effectively, followed by medium (10 μm) and small (1 μm). Consistent with our results from climbing beetles, force measurements on freshly severed legs revealed larger detachment forces of medium particles from adhesive pads compared to a flat surface, possibly due to interlocking between fibres. By contrast, dock leaves showed an overall larger affinity to the beads and thus reduced the need for cleaning. Self-cleaning through slippage provides a mechanism robust to particle size and may inspire solutions for artificial adhesives.

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DOI Project Page [BibTex]

DOI Project Page [BibTex]


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Non-Equilibrium Assembly of Light-Activated Colloidal Mixtures

Singh, D. P., Choudhury, U., Fischer, P., Mark, A. G.

Advanced Materials, 29, pages: 1701328, June 2017, 32 (article)

Abstract
The collective phenomena exhibited by artificial active matter systems present novel routes to fabricating out-of-equilibrium microscale assemblies. Here, the crystallization of passive silica colloids into well-controlled 2D assemblies is shown, which is directed by a small number of self-propelled active colloids. The active colloids are titania–silica Janus particles that are propelled when illuminated by UV light. The strength of the attractive interaction and thus the extent of the assembled clusters can be regulated by the light intensity. A remarkably small number of the active colloids is sufficient to induce the assembly of the dynamic crystals. The approach produces rationally designed colloidal clusters and crystals with controllable sizes, shapes, and symmetries. This multicomponent active matter system offers the possibility of obtaining structures and assemblies that cannot be found in equilibrium systems.

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link (url) DOI [BibTex]


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Yield prediction in parallel homogeneous assembly

Ipparthi, D., Winslow, A., Sitti, M., Dorigo, M., Mastrangeli, M.

Soft Matter, 13, pages: 7595-7608, The Royal Society of Chemistry, June 2017 (article)

Abstract
We investigate the parallel assembly of two-dimensional{,} geometrically-closed modular target structures out of homogeneous sets of macroscopic components of varying anisotropy. The yield predicted by a chemical reaction network (CRN)-based model is quantitatively shown to reproduce experimental results over a large set of conditions. Scaling laws for parallel assembling systems are then derived from the model. By extending the validity of the CRN-based modelling{,} this work prompts analysis and solutions to the incompatible substructure problem.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Nanodiamonds That Swim

Kim, J. T., Choudhury, U., Hyeon-Ho, J., Fischer, P.

Advanced Materials, 29(30):1701024, June 2017, Back Cover (article)

Abstract
Nanodiamonds are emerging as nanoscale quantum probes for bio-sensing and imaging. This necessitates the development of new methods to accurately manipulate their position and orientation in aqueous solutions. The realization of an “active” nanodiamond (ND) swimmer in fluids, composed of a ND crystal containing nitrogen vacancy centers and a light-driven self-thermophoretic micromotor, is reported. The swimmer is propelled by a local temperature gradient created by laser illumination on its metal-coated side. Its locomotion—from translational to rotational motion—is successfully controlled by shape-dependent hydrodynamic interactions. The precise engineering of the swimmer's geometry is achieved by self-assembly combined with physical vapor shadow growth. The optical addressability of the suspended ND swimmers is demonstrated by observing the electron spin resonance in the presence of magnetic fields. Active motion at the nanoscale enables new sensing capabilities combined with active transport including, potentially, in living organisms.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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Three‐dimensional patterning in biomedicine: Importance and applications in neuropharmacology

Ajay, V. S., Tanmay, G., Madu, B., Byung‐Wook, P., Thomas, E., Metin, S.

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 106(3):1369-1382, June 2017 (article)

Abstract
Abstract Nature manufactures biological systems in three dimensions with precisely controlled spatiotemporal profiles on hierarchical length and time scales. In this article, we review 3D patterning of biological systems on synthetic platforms for neuropharmacological applications. We briefly describe 3D versus 2D chemical and topographical patterning methods and their limitations. Subsequently, an overview of introducing a third dimension in neuropharmacological research with delineation of chemical and topographical roles is presented. Finally, toward the end of this article, an explanation of how 3D patterning has played a pivotal role in relevant fields of neuropharmacology to understand neurophysiology during development, normal health, and disease conditions is described. The future prospects of organs‐on‐a‐‐like devices to mimic patterned blood–brain barrier in the context of neurotherapeutic discovery and development for the prioritization of lead candidates, membrane potential, and toxicity testing are also described. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1369–1382, 2018.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]