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2019


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

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

ACS Nano, March 2019 (article)

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

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link (url) DOI [BibTex]


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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]


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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]


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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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Microrobotics and Microorganisms: Biohybrid Autonomous Cellular Robots

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

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

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[BibTex]

[BibTex]


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X-ray Optics Fabrication Using Unorthodox Approaches

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

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

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[BibTex]

[BibTex]


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The near and far of a pair of magnetic capillary disks

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

Soft Matter, 2019 (article)

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[BibTex]

[BibTex]


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

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

Toxicology Mechanisms and Methods, 2019 (article)

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[BibTex]

[BibTex]


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Graphene oxide synergistically enhances antibiotic efficacy in Vancomycin resistance Staphylococcus aureus

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

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

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[BibTex]

[BibTex]


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Microfluidics Integrated Lithography‐Free Nanophotonic Biosensor for the Detection of Small Molecules

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

Advanced Optical Materials, 2019 (article)

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[BibTex]

[BibTex]


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Mobile microrobots for active therapeutic delivery

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

Advanced Therapeutics, Wiley Online Library, 2019 (article)

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[BibTex]

[BibTex]


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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)

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[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]


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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.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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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.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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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]


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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.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


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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.

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link (url) DOI Project Page [BibTex]

link (url) DOI Project Page [BibTex]


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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.

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link (url) DOI Project Page [BibTex]


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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]


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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.

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link (url) Project Page [BibTex]


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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.

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link (url) Project Page [BibTex]


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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.

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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]


Thumb xl kim et al 2017 advanced materials
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]


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Tail-Assisted Mobility and Stability Enhancement in Yaw/Pitch Motions of a Water-Running Robot

Kim, H., Sitti, M., Seo, T.

IEEE/ASME Transactions on Mechatronics, 22(3):1207–1217, IEEE, June 2017 (article)

Abstract
Water-running robots have been developed inspired by a basilisk lizard, which demonstrates highly agile, stable, and energy-efficient locomotion on water surfaces. Current water-running robots are not as stable and agile as their biological counterparts. This study shows how the stability of a water-running robot in the pitch direction can be improved by using an active tail to enable increased propulsion. The mobility of the robot is also increased. To generate force in the pitch and yaw directions, a two-degrees-of-freedom tail is implemented with two circular plates to provide drag. We developed two types of dynamic models for pitch and yaw behavior, and the results are recursively calculated by considering the correlation between the models. The relationship between pitch motion and propulsion was analyzed by simulations. The steering behavior of the robot is also validated while considering the pitch behavior. Experiments were conducted to verify the simulation results.

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DOI [BibTex]

DOI [BibTex]


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Propulsion and Chemotaxis in Bacteria-Driven Microswimmers

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

Advanced Science, 4(9):1700109, May 2017 (article)

Abstract
Despite the large body of experimental work recently on biohybrid microsystems, few studies have focused on theoretical modeling of such systems, which is essential to understand their underlying functioning mechanisms and hence design them optimally for a given application task. Therefore, this study focuses on developing a mathematical model to describe the 3D motion and chemotaxis of a type of widely studied biohybrid microswimmer, where spherical microbeads are driven by multiple attached bacteria. The model is developed based on the biophysical observations of the experimental system and is validated by comparing the model simulation with experimental 3D swimming trajectories and other motility characteristics, including mean squared displacement, speed, diffusivity, and turn angle. The chemotaxis modeling results of the microswimmers also agree well with the experiments, where a collective chemotactic behavior among multiple bacteria is observed. The simulation result implies that such collective chemotaxis behavior is due to a synchronized signaling pathway across the bacteria attached to the same microswimmer. Furthermore, the dependencies of the motility and chemotaxis of the microswimmers on certain system parameters, such as the chemoattractant concentration gradient, swimmer body size, and number of attached bacteria, toward an optimized design of such biohybrid system are studied. The optimized microswimmers would be used in targeted cargo, e.g., drug, imaging agent, gene, and RNA, transport and delivery inside the stagnant or low-velocity fluids of the human body as one of their potential biomedical applications.

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DOI Project Page [BibTex]


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Dynamic and programmable self-assembly of micro-rafts at the air-water interface

Wang, W., Giltinan, J., Zakharchenko, S., Sitti, M.

Science Advances, 3(5):e1602522, American Association for the Advancement of Science, May 2017 (article)

Abstract
Dynamic self-assembled material systems constantly consume energy to maintain their spatiotemporal structures and functions. Programmable self-assembly translates information from individual parts to the collective whole. Combining dynamic and programmable self-assembly in a single platform opens up the possibilities to investigate both types of self-assembly simultaneously and to explore their synergy. This task is challenging because of the difficulty in finding suitable interactions that are both dissipative and programmable. We present a dynamic and programmable self-assembling material system consisting of spinning at the air-water interface circular magnetic micro-rafts of radius 50 μm and with cosinusoidal edge-height profiles. The cosinusoidal edge-height profiles not only create a net dissipative capillary repulsion that is sustained by continuous torque input but also enable directional assembly of micro-rafts. We uncover the layered arrangement of micro-rafts in the patterns formed by dynamic self-assembly and offer mechanistic insights through a physical model and geometric analysis. Furthermore, we demonstrate programmable self-assembly and show that a 4-fold rotational symmetry encoded in individual micro-rafts translates into 90° bending angles and square-based tiling in the assembled structures of micro-rafts. We anticipate that our dynamic and programmable material system will serve as a model system for studying nonequilibrium dynamics and statistical mechanics in the future

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DOI [BibTex]

DOI [BibTex]


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Presentation of functional groups on self-assembled supramolecular peptide nanofibers mimicking glycosaminoglycans for directed mesenchymal stem cell differentiation

Yasa, O., Uysal, O., Ekiz, M. S., Guler, M. O., Tekinay, A. B.

J. Mater. Chem. B, 5, pages: 4890-4900, The Royal Society of Chemistry, May 2017 (article)

Abstract
Organizational complexity and functional diversity of the extracellular matrix regulate cellular behaviors. The extracellular matrix is composed of various proteins in the form of proteoglycans{,} glycoproteins{,} and nanofibers whose types and combinations change depending on the tissue type. Proteoglycans{,} which are proteins that are covalently attached to glycosaminoglycans{,} contribute to the complexity of the microenvironment of the cells. The sulfation degree of the glycosaminoglycans is an important and distinct feature at specific developmental stages and tissue types. Peptide amphiphile nanofibers can mimic natural glycosaminoglycans and/or proteoglycans{,} and they form a synthetic nanofibrous microenvironment where cells can proliferate and differentiate towards different lineages. In this study{,} peptide nanofibers were used to provide varying degrees of sulfonation mimicking the natural glycosaminoglycans by forming a microenvironment for the survival and differentiation of stem cells. The effects of glucose{,} carboxylate{,} and sulfonate groups on the peptide nanofibers were investigated by considering the changes in the differentiation profiles of rat mesenchymal stem cells in the absence of any specific differentiation inducers in the culture medium. The results showed that a higher sulfonate-to-glucose ratio is associated with adipogenic differentiation and a higher carboxylate-to-glucose ratio is associated with osteochondrogenic differentiation of the rat mesenchymal stem cells. Overall{,} these results demonstrate that supramolecular peptide nanosystems can be used to understand the fine-tunings of the extracellular matrix such as sulfation profile on specific cell types.

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link (url) DOI [BibTex]

link (url) DOI [BibTex]


Thumb xl drotlef et al 2017 advanced materials
Bioinspired Composite Microfibers for Skin Adhesion and Signal Amplification of Wearable Sensors

Drotlef, D., Amjadi, M., Yunusa, M., Sitti, M.

Advanced Materials, 29(28):1701353, May 2017, Back Cover (article)

Abstract
A facile approach is proposed for superior conformation and adhesion of wearable sensors to dry and wet skin. Bioinspired skin-adhesive films are composed of elastomeric microfibers decorated with conformal and mushroom-shaped vinylsiloxane tips. Strong skin adhesion is achieved by crosslinking the viscous vinylsiloxane tips directly on the skin surface. Furthermore, composite microfibrillar adhesive films possess a high adhesion strength of 18 kPa due to the excellent shape adaptation of the vinylsiloxane tips to the multiscale roughness of the skin. As a utility of the skin-adhesive films in wearable-device applications, they are integrated with wearable strain sensors for respiratory and heart-rate monitoring. The signal-to-noise ratio of the strain sensor is significantly improved to 59.7 because of the considerable signal amplification of microfibrillar skin-adhesive films.

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DOI [BibTex]


Thumb xl mostaghaci et al 2017 advanced science
Bioadhesive Bacterial Microswimmers for Targeted Drug Delivery in the Urinary and Gastrointestinal Tracts

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

Advanced Science, 4(6):1700058, May 2017 (article)

Abstract
Bacteria-driven biohybrid microswimmers (bacteriabots), which integrate motile bacterial cells and functional synthetic cargo parts (e.g., microparticles encapsulating drug), are recently studied for targeted drug delivery. However, adhesion of such bacteriabots to the tissues on the site of a disease (which can increase the drug delivery efficiency) is not studied yet. Here, this paper proposes an approach to attach bacteriabots to certain types of epithelial cells (expressing mannose on the membrane), based on the affinity between lectin molecules on the tip of bacterial type I pili and mannose molecules on the epithelial cells. It is shown that the bacteria can anchor their cargo particles to mannose-functionalized surfaces and mannose-expressing cells (ATCC HTB-9) using the lectin–mannose bond. The attachment mechanism is confirmed by comparing the adhesion of bacteriabots fabricated from bacterial strains with or without type I pili to mannose-covered surfaces and cells. The proposed bioadhesive motile system can be further improved by expressing more specific adhesion moieties on the membrane of the bacteria.

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DOI Project Page [BibTex]


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Six Degree-of-Freedom Localization of Endoscopic Capsule Robots using Recurrent Neural Networks embedded into a Convolutional Neural Network

Turan, M., Abdullah, A., Jamiruddin, R., Araujo, H., Konukoglu, E., Sitti, M.

arXiv preprint arXiv:1705.06196, May 2017 (article)

Abstract
Since its development, ingestible wireless endoscopy is considered to be a painless diagnostic method to detect a number of diseases inside GI tract. Medical related engineering companies have made significant improvements in this technology in last decade; however, some major limitations still residue. Localization of the next generation steerable endoscopic capsule robot in six degreeof-freedom (DoF) and active motion control are some of these limitations. The significance of localization capability concerns with the doctors correct diagnosis of the disease area. This paper presents a very robust 6-DoF localization method based on supervised training of an architecture consisting of recurrent networks (RNN) embedded into a convolutional neural network (CNN) to make use of both just-in-moment information obtained by CNN and correlative information across frames obtained by RNN. To our knowledge, our idea of embedding RNNs into a CNN architecture is for the first time proposed in literature. The experimental results show that the proposed RNN-in-CNN architecture performs very well for endoscopic capsule robot localization in cases vignetting, reflection distortions, noise, sudden camera movements and lack of distinguishable features.

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DOI Project Page [BibTex]


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Controllable load sharing for soft adhesive interfaces on three-dimensional surfaces

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

Proceedings of the National Academy of Sciences, 114(22):E4344–E4353, National Acad Sciences, May 2017 (article)

Abstract
For adhering to three-dimensional (3D) surfaces or objects, current adhesion systems are limited by a fundamental trade-off between 3D surface conformability and high adhesion strength. This limitation arises from the need for a soft, mechanically compliant interface, which enables conformability to nonflat and irregularly shaped surfaces but significantly reduces the interfacial fracture strength. In this work, we overcome this trade-off with an adhesion-based soft-gripping system that exhibits enhanced fracture strength without sacrificing conformability to nonplanar 3D surfaces. Composed of a gecko-inspired elastomeric microfibrillar adhesive membrane supported by a pressure-controlled deformable gripper body, the proposed soft-gripping system controls the bonding strength by changing its internal pressure and exploiting the mechanics of interfacial equal load sharing. The soft adhesion system can use up to ∼26% of the maximum adhesion of the fibrillar membrane, which is 14× higher than the adhering membrane without load sharing. Our proposed load-sharing method suggests a paradigm for soft adhesion-based gripping and transfer-printing systems that achieves area scaling similar to that of a natural gecko footpad.

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DOI Project Page [BibTex]

DOI Project Page [BibTex]


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A Non-Rigid Map Fusion-Based RGB-Depth SLAM Method for Endoscopic Capsule Robots

Turan, M., Almalioglu, Y., Araujo, H., Konukoglu, E., Sitti, M.

arXiv preprint arXiv:1705.05444, May 2017 (article)

Abstract
In the gastrointestinal (GI) tract endoscopy field, ingestible wireless capsule endoscopy is considered as a minimally invasive novel diagnostic technology to inspect the entire GI tract and to diagnose various diseases and pathologies. Since the development of this technology, medical device companies and many groups have made significant progress to turn such passive capsule endoscopes into robotic active capsule endoscopes to achieve almost all functions of current active flexible endoscopes. However, the use of robotic capsule endoscopy still has some challenges. One such challenge is the precise localization of such active devices in 3D world, which is essential for a precise three-dimensional (3D) mapping of the inner organ. A reliable 3D map of the explored inner organ could assist the doctors to make more intuitive and correct diagnosis. In this paper, we propose to our knowledge for the first time in literature a visual simultaneous localization and mapping (SLAM) method specifically developed for endoscopic capsule robots. The proposed RGB-Depth SLAM method is capable of capturing comprehensive dense globally consistent surfel-based maps of the inner organs explored by an endoscopic capsule robot in real time. This is achieved by using dense frame-to-model camera tracking and windowed surfelbased fusion coupled with frequent model refinement through non-rigid surface deformations.

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link (url) Project Page [BibTex]

link (url) Project Page [BibTex]


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Hydrophobic pinning with copper nanowhiskers leads to bactericidal properties

Singh, A. V., Baylan, S., Park, B., Richter, G., Sitti, M.

PloS One, 12(4):e0175428, Public Library of Science, April 2017 (article)

Abstract
The considerable morbidity associated with hospitalized patients and clinics in developed countries due to biofilm formation on biomedical implants and surgical instruments is a heavy economic burden. An alternative to chemically treated surfaces for bactericidal activity started emerging from micro/nanoscale topographical cues in the last decade. Here, we demonstrate a putative antibacterial surface using copper nanowhiskers deposited by molecular beam epitaxy. Furthermore, the control of biological response is based on hydrophobic pinning of water droplets in the Wenzel regime, causing mechanical injury and cell death. Scanning electron microscopy images revealed the details of the surface morphology and non-contact mode laser scanning of the surface revealed the microtopography-associated quantitative parameters. Introducing the bacterial culture over nanowhiskers produces mechanical injury to cells, leading to a reduction in cell density over time due to local pinning of culture medium to whisker surfaces. Extended culture to 72 hours to observe biofilm formation revealed biofilm inhibition with scattered microcolonies and significantly reduced biovolume on nanowhiskers. Therefore, surfaces patterned with copper nanowhiskers can serve as potential antibiofilm surfaces. The topography-based antibacterial surfaces introduce a novel prospect in developing mechanoresponsive nanobiomaterials to reduce the risk of medical device biofilm-associated infections, contrary to chemical leaching of copper as a traditional bactericidal agent.

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link (url) [BibTex]

link (url) [BibTex]


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Soft 3D-Printed Phantom of the Human Kidney with Collecting System

Adams, F., Qiu, T., Mark, A., Fritz, B., Kramer, L., Schlager, D., Wetterauer, U., Miernik, A., Fischer, P.

Ann. of Biomed. Eng., 45(4):963-972, April 2017 (article)

Abstract
Organ models are used for planning and simulation of operations, developing new surgical instruments, and training purposes. There is a substantial demand for in vitro organ phantoms, especially in urological surgery. Animal models and existing simulator systems poorly mimic the detailed morphology and the physical properties of human organs. In this paper, we report a novel fabrication process to make a human kidney phantom with realistic anatomical structures and physical properties. The detailed anatomical structure was directly acquired from high resolution CT data sets of human cadaveric kidneys. The soft phantoms were constructed using a novel technique that combines 3D wax printing and polymer molding. Anatomical details and material properties of the phantoms were validated in detail by CT scan, ultrasound, and endoscopy. CT reconstruction, ultrasound examination, and endoscopy showed that the designed phantom mimics a real kidney's detailed anatomy and correctly corresponds to the targeted human cadaver's upper urinary tract. Soft materials with a tensile modulus of 0.8-1.5 MPa as well as biocompatible hydrogels were used to mimic human kidney tissues. We developed a method of constructing 3D organ models from medical imaging data using a 3D wax printing and molding process. This method is cost-effective means for obtaining a reproducible and robust model suitable for surgical simulation and training purposes.

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DOI Project Page [BibTex]

DOI Project Page [BibTex]


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Biohybrid microtube swimmers driven by single captured bacteria

Stanton, M. M., Park, B., Miguel-López, A., Ma, X., Sitti, M., Sánchez, S.

Small, 13(19), March 2017 (article)

Abstract
Bacteria biohybrids employ the motility and power of swimming bacteria to carry and maneuver microscale particles. They have the potential to perform microdrug and cargo delivery in vivo, but have been limited by poor design, reduced swimming capabilities, and impeded functionality. To address these challenge, motile Escherichia coli are captured inside electropolymerized microtubes, exhibiting the first report of a bacteria microswimmer that does not utilize a spherical particle chassis. Single bacterium becomes partially trapped within the tube and becomes a bioengine to push the microtube though biological media. Microtubes are modified with “smart” material properties for motion control, including a bacteria-attractant polydopamine inner layer, addition of magnetic components for external guidance, and a biochemical kill trigger to cease bacterium swimming on demand. Swimming dynamics of the bacteria biohybrid are quantified by comparing “length of protrusion” of bacteria from the microtubes with respect to changes in angular autocorrelation and swimmer mean squared displacement. The multifunctional microtubular swimmers present a new generation of biocompatible micromotors toward future microbiorobots and minimally invasive medical applications.

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DOI Project Page [BibTex]

DOI Project Page [BibTex]


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Sticky Solution Provides Grip for the First Robotic Pollinator

Amador, G. J., Hu, D. L.

Chem, 2(2):162 - 164, Febuary 2017 (article)

Abstract
Bees, move over. A lily has been pollinated by a remote-controlled flying robot. The robot is hairy, just like a real bee, and sticks to pollen by virtue of an ionic liquid gel, whose fabrication is discussed by Svetlana Chechetka et al. in this issue of Chem.

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link (url) DOI [BibTex]


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Pattern formation and collective effects in populations of magnetic microswimmers

Vach, P. J., (Walker) Schamel, D., Fischer, P., Fratzl, P., Faivre, D.

J. of Phys. D: Appl. Phys., 50(11):11LT03, Febuary 2017 (article)

Abstract
Self-propelled particles are one prototype of synthetic active matter used to understand complex biological processes, such as the coordination of movement in bacterial colonies or schools of fishes. Collective patterns such as clusters were observed for such systems, reproducing features of biological organization. However, one limitation of this model is that the synthetic assemblies are made of identical individuals. Here we introduce an active system based on magnetic particles at colloidal scales. We use identical but also randomly-shaped magnetic micropropellers and show that they exhibit dynamic and reversible pattern formation.

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DOI [BibTex]

DOI [BibTex]


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On-chip enzymatic microbiofuel cell-powered integrated circuits

Mark, A. G., Suraniti, E., Roche, J., Richter, H., Kuhn, A., Mano, N., Fischer, P.

Lab on a Chip, 17(10):1761-1768, Febuary 2017, Recent HOT Article (article)

Abstract
A variety of diagnostic and therapeutic medical technologies rely on long term implantation of an electronic device to monitor or regulate a patient's condition. One proposed approach to powering these devices is to use a biofuel cell to convert the chemical energy from blood nutrients into electrical current to supply the electronics. We present here an enzymatic microbiofuel cell whose electrodes are directly integrated into a digital electronic circuit. Glucose oxidizing and oxygen reducing enzymes are immobilized on microelectrodes of an application specific integrated circuit (ASIC) using redox hydrogels to produce an enzymatic biofuel cell, capable of harvesting electrical power from just a single droplet of 5 mM glucose solution. Optimisation of the fuel cell voltage and power to match the requirements of the electronics allow self-powered operation of the on-board digital circuitry. This study represents a step towards implantable self-powered electronic devices that gather their energy from physiological fluids.

Recent HOT Article.

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DOI [BibTex]

DOI [BibTex]


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Strong Rotational Anisotropies Affect Nonlinear Chiral Metamaterials

Hooper, D. C., Mark, A. G., Kuppe, C., Collins, J. T., Fischer, P., Valev, V. K.

Advanced Materials, 29(13):1605110, January 2017 (article)

Abstract
Masked by rotational anisotropies, the nonlinear chiroptical response of a metamaterial is initially completely inaccessible. Upon rotating the sample the chiral information emerges. These results highlight the need for a general method to extract the true chiral contributions to the nonlinear optical signal, which would be hugely valuable in the present context of increasingly complex chiral meta/nanomaterials.

pf

DOI [BibTex]

DOI [BibTex]