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87 results (View BibTeX file of all listed publications)

2017

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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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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]

pi Turan, M., Shabbir, J., Araujo, H., Konukoglu, E., Sitti, M. A deep learning based fusion of RGB camera information and magnetic localization information for endoscopic capsule robots International Journal of Intelligent Robotics and Applications, 1(4):442-450, December 2017 (article)

link (url) DOI [BibTex]

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Evaluation of High-Fidelity Simulation as a Training Tool in Transoral Robotic Surgery

Bur, A. M., Gomez, E. D., Newman, J. G., Weinstein, G. S., Bert W. O’Malley, J., Rassekh, C. H., Kuchenbecker, K. J.

Laryngoscope, 127(12):2790-2795, December 2017 (article)

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DOI [BibTex]

hi Bur, A. M., Gomez, E. D., Newman, J. G., Weinstein, G. S., Bert W. O’Malley, J., Rassekh, C. H., Kuchenbecker, K. J. Evaluation of High-Fidelity Simulation as a Training Tool in Transoral Robotic Surgery Laryngoscope, 127(12):2790-2795, December 2017 (article)

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]

pi Ricotti, L., Trimmer, B., Feinberg, A. W., Raman, R., Parker, K. K., Bashir, R., Sitti, M., Martel, S., Dario, P., Menciassi, A. Biohybrid actuators for robotics: A review of devices actuated by living cells Science Robotics, 2(12), Science Robotics, November 2017 (article)

link (url) DOI [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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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.

pi

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]

pi Stanton, M. M., Park, B., Vilela, D., Bente, K., Faivre, D., Sitti, M., Sánchez, S. Magnetotactic Bacteria Powered Biohybrids Target E. coli Biofilms ACS Nano, 0(0):null, September 2017, PMID: 28933815 (article)

link (url) DOI Project Page [BibTex]

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Using Contact Forces and Robot Arm Accelerations to Automatically Rate Surgeon Skill at Peg Transfer

Brown, J. D., O’Brien, C. E., Leung, S. C., Dumon, K. R., Lee, D. I., Kuchenbecker, K. J.

IEEE Transactions on Biomedical Engineering, 64(9):2263-2275, September 2017 (article)

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link (url) DOI [BibTex]

hi Brown, J. D., O’Brien, C. E., Leung, S. C., Dumon, K. R., Lee, D. I., Kuchenbecker, K. J. Using Contact Forces and Robot Arm Accelerations to Automatically Rate Surgeon Skill at Peg Transfer IEEE Transactions on Biomedical Engineering, 64(9):2263-2275, September 2017 (article)

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]

pi Turan, M., Yigit Pilavci, Y., Ganiyusufoglu, I., Araujo, H., Konukoglu, E., Sitti, M. Sparse-then-Dense Alignment based 3D Map Reconstruction Method for Endoscopic Capsule Robots ArXiv e-prints, August 2017 (article)

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]

pi Ipparthi, D., Mastrangeli, M., Winslow, A. Dipole codes attractively encode glue functions Theoretical Computer Science, 671, pages: 19 - 25, August 2017, Computational Self-Assembly (article)

link (url) DOI [BibTex]

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Ungrounded Haptic Augmented Reality System for Displaying Texture and Friction

Culbertson, H., Kuchenbecker, K. J.

IEEE/ASME Transactions on Mechatronics, 22(4):1839-1849, August 2017 (article)

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link (url) DOI [BibTex]

hi Culbertson, H., Kuchenbecker, K. J. Ungrounded Haptic Augmented Reality System for Displaying Texture and Friction IEEE/ASME Transactions on Mechatronics, 22(4):1839-1849, August 2017 (article)

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]

pi Kim, M., Alapan, Y., Adhikari, A., Little, J. A., Gurkan, U. A. Hypoxia‐enhanced adhesion of red blood cells in microscale flow Microcirculation, 24(5):e12374, July 2017 (article)

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]

pi Amador, G., Endlein, T., Sitti, M. Soiled adhesive pads shear clean by slipping: a robust self-cleaning mechanism in climbing beetles Journal of The Royal Society Interface, 14(131):20170134, The Royal Society, June 2017 (article)

DOI Project Page [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]

pi Ipparthi, D., Winslow, A., Sitti, M., Dorigo, M., Mastrangeli, M. Yield prediction in parallel homogeneous assembly Soft Matter, 13, pages: 7595-7608, The Royal Society of Chemistry, June 2017 (article)

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]

pi Ajay, V. S., Tanmay, G., Madu, B., Byung‐Wook, P., Thomas, E., Metin, S. Three‐dimensional patterning in biomedicine: Importance and applications in neuropharmacology Journal of Biomedical Materials Research Part B: Applied Biomaterials, 106(3):1369-1382, June 2017 (article)

link (url) DOI [BibTex]

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Perception of Force and Stiffness in the Presence of Low-Frequency Haptic Noise

Gurari, N., Okamura, A. M., Kuchenbecker, K. J.

PLoS ONE, 12(6):e0178605, June 2017 (article)

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link (url) DOI [BibTex]

hi Gurari, N., Okamura, A. M., Kuchenbecker, K. J. Perception of Force and Stiffness in the Presence of Low-Frequency Haptic Noise PLoS ONE, 12(6):e0178605, June 2017 (article)

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]

pi Kim, H., Sitti, M., Seo, T. Tail-Assisted Mobility and Stability Enhancement in Yaw/Pitch Motions of a Water-Running Robot IEEE/ASME Transactions on Mechatronics, 22(3):1207–1217, IEEE, June 2017 (article)

DOI [BibTex]

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Evaluation of a Vibrotactile Simulator for Dental Caries Detection

Kuchenbecker, K. J., Parajon, R., Maggio, M. P.

Simulation in Healthcare, 12(3):148-156, June 2017 (article)

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DOI [BibTex]

hi Kuchenbecker, K. J., Parajon, R., Maggio, M. P. Evaluation of a Vibrotactile Simulator for Dental Caries Detection Simulation in Healthcare, 12(3):148-156, June 2017 (article)

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]

pi Wang, W., Giltinan, J., Zakharchenko, S., Sitti, M. Dynamic and programmable self-assembly of micro-rafts at the air-water interface Science Advances, 3(5):e1602522, American Association for the Advancement of Science, May 2017 (article)

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]

pi Yasa, O., Uysal, O., Ekiz, M. S., Guler, M. O., Tekinay, A. B. Presentation of functional groups on self-assembled supramolecular peptide nanofibers mimicking glycosaminoglycans for directed mesenchymal stem cell differentiation J. Mater. Chem. B, 5, pages: 4890-4900, The Royal Society of Chemistry, May 2017 (article)

link (url) DOI [BibTex]

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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]

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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.

pi

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.

pi

DOI Project Page [BibTex]

pi Song, S., Drotlef, D., Majidi, C., Sitti, M. Controllable load sharing for soft adhesive interfaces on three-dimensional surfaces Proceedings of the National Academy of Sciences, 114(22):E4344–E4353, National Acad Sciences, May 2017 (article)

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.

pi

link (url) Project Page [BibTex]

pi Turan, M., Almalioglu, Y., Araujo, H., Konukoglu, E., Sitti, M. A Non-Rigid Map Fusion-Based RGB-Depth SLAM Method for Endoscopic Capsule Robots arXiv preprint arXiv:1705.05444, May 2017 (article)

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.

pi

link (url) [BibTex]

pi Singh, A. V., Baylan, S., Park, B., Richter, G., Sitti, M. Hydrophobic pinning with copper nanowhiskers leads to bactericidal properties PloS One, 12(4):e0175428, Public Library of Science, April 2017 (article)

link (url) [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.

pi

DOI Project Page [BibTex]

pi Stanton, M. M., Park, B., Miguel-López, A., Ma, X., Sitti, M., Sánchez, S. Biohybrid microtube swimmers driven by single captured bacteria Small, 13(19), March 2017 (article)

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.

pi

link (url) DOI [BibTex]

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Rubbing Against Blood Clots Using Helical Robots: Modeling and In Vitro Experimental Validation

Khalil, I. S., Tabak, A. F., Sadek, K., Mahdy, D., Hamdi, N., Sitti, M.

IEEE Robotics and Automation Letters, 2(2):927-934, IEEE, January 2017 (article)

Abstract
The risk of side effects from thrombolytic agents can be minimized by using smaller doses, assisted by mechanical rubbing against blood clots using helical robots. Quantifying this observation, we study the influence of rubbing against clots on their removal rate in vitro. First, we present a hydrodynamic model of the helical robot based on the resistive-force theory to investigate the rubbing behavior of the clots using robot driven by two rotating dipole fields. Second, we experimentally evaluate the influence of the rubbing on the removal rate of the blood clots. Not only do we find that the removal rate of mechanical rubbing (-0.56 ± 0.27 mm3 /min) is approximately three times greater than the dissolution rate of chemical lysis using streptokinase (-0.17 ± 0.032 mm3/min), but we also show that this removal rate can be controlled via the rubbing speed of the robot.

pi

DOI [BibTex]

pi Khalil, I. S., Tabak, A. F., Sadek, K., Mahdy, D., Hamdi, N., Sitti, M. Rubbing Against Blood Clots Using Helical Robots: Modeling and In Vitro Experimental Validation IEEE Robotics and Automation Letters, 2(2):927-934, IEEE, January 2017 (article)

DOI [BibTex]

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Nanoscale topographical control of capillary assembly of nanoparticles

Flauraud, V., Mastrangeli, M., Bernasconi, G., Butet, J., Alexander, D., Shahrabi, E., Martin, O., Brugger, J.

Scientific Reports, Nature Nanotechnology, 12, pages: 73-80, January 2017 (article)

Abstract
Predetermined and selective placement of nanoparticles onto large-area substrates with nanometre-scale precision is essential to harness the unique properties of nanoparticle assemblies, in particular for functional optical and electro-optical nanodevices. Unfortunately, such high spatial organization is currently beyond the reach of top-down nanofabrication techniques alone. Here, we demonstrate that topographic features comprising lithographed funnelled traps and auxiliary sidewalls on a solid substrate can deterministically direct the capillary assembly of Au nanorods to attain simultaneous control of position, orientation and interparticle distance at the nanometre level. We report up to 100% assembly yield over centimetre-scale substrates. We achieve this by optimizing the three sequential stages of capillary nanoparticle assembly: insertion of nanorods into the traps, resilience against the receding suspension front and drying of the residual solvent. Finally, using electron energy-loss spectroscopy we characterize the spectral response and near-field properties of spatially programmable Au nanorod dimers, highlighting the opportunities for precise tunability of the plasmonic modes in larger assemblies.

pi

DOI [BibTex]

pi Flauraud, V., Mastrangeli, M., Bernasconi, G., Butet, J., Alexander, D., Shahrabi, E., Martin, O., Brugger, J. Nanoscale topographical control of capillary assembly of nanoparticles Scientific Reports, Nature Nanotechnology, 12, pages: 73-80, January 2017 (article)

DOI [BibTex]

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Importance of Matching Physical Friction, Hardness, and Texture in Creating Realistic Haptic Virtual Surfaces

Culbertson, H., Kuchenbecker, K. J.

IEEE Transactions on Haptics, 10(1):63-74, January 2017 (article)

hi

[BibTex]

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Effects of Grip-Force, Contact, and Acceleration Feedback on a Teleoperated Pick-and-Place Task

Khurshid, R. P., Fitter, N. T., Fedalei, E. A., Kuchenbecker, K. J.

IEEE Transactions on Haptics, 10(1):40-53, January 2017 (article)

hi

[BibTex]

hi Khurshid, R. P., Fitter, N. T., Fedalei, E. A., Kuchenbecker, K. J. Effects of Grip-Force, Contact, and Acceleration Feedback on a Teleoperated Pick-and-Place Task IEEE Transactions on Haptics, 10(1):40-53, January 2017 (article)

[BibTex]

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Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality

Raymond, M. J., Ray, P., Kaur, G., Fredericks, M., Singh, A. V., Wan, L. Q.

Cellular and Molecular Bioengineering, 10(1):63-74, 2017 (article)

Abstract
Intrinsic cell chirality has been implicated in the left--right (LR) asymmetry of embryonic development. Impaired cell chirality could lead to severe birth defects in laterality. Previously, we detected cell chirality with an in vitro micropatterning system. Here, we demonstrate for the first time that chirality can be quantified as the coordination of multiaxial polarization of individual cells and nuclei. Using an object labeling, connected component based method, we characterized cell chirality based on cell and nuclear shape polarization and nuclear positioning of each cell in multicellular patterns of epithelial cells. We found that the cells adopted a LR bias the boundaries by positioning the sharp end towards the leading edge and leaving the nucleus at the rear. This behavior is consistent with the directional migration observed previously on the boundary of micropatterns. Although the nucleus is chirally aligned, it is not strongly biased towards or away from the boundary. As the result of the rear positioning of nuclei, the nuclear positioning has an opposite chirality to that of cell alignment. Overall, our results have revealed deep insights of chiral morphogenesis as the coordination of multiaxial polarization at the cellular and subcellular levels.

pi

link (url) DOI [BibTex]

pi Raymond, M. J., Ray, P., Kaur, G., Fredericks, M., Singh, A. V., Wan, L. Q. Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality Cellular and Molecular Bioengineering, 10(1):63-74, 2017 (article)

link (url) DOI [BibTex]

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Gene delivery particle engineering strategies for shape-dependent targeting of cells and tissues.

Kozielski, K., Sitti, M.

Current Gene Therapy, 17, 2017 (article)

Abstract
Background: Successful gene delivery requires overcoming both systemic and intracellular obstacles before the nucleic acid cargo can successfully reach its tissue and subcellular target location. Materials & Methods: Non-viral mechanisms to enable targeting while avoiding off-target delivery have arisen via biological, chemical, and physical engineering strategies. Discussion: Herein we will discuss the physical parameters in particle design that promote tissue- and cell-targeted delivery of genetic cargo. We will discuss systemic concerns, such as circulation, tissue localization, and clearance, as well as cell-scale obstacles, such as cellular uptake and nucleic acid packaging. Conclusion: In particular, we will focus on engineering particle shape and size in order to enhance delivery and promote precise targeting. We will also address methods to program or change particle shape in situ using environmentally triggered cues.

pi

DOI [BibTex]

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Multi-fractal characterization of bacterial swimming dynamics: a case study on real and simulated Serratia marcescens

Koorehdavoudi, H., Bogdan, P., Wei, G., Marculescu, R., Zhuang, J., Carlsen, R. W., Sitti, M.

Proceedings of the Royal Society of London A: Mathematical, Physical and Engineering Sciences, 473(2203), The Royal Society, 2017 (article)

Abstract
To add to the current state of knowledge about bacterial swimming dynamics, in this paper, we study the fractal swimming dynamics of populations of Serratia marcescens bacteria both in vitro and in silico, while accounting for realistic conditions like volume exclusion, chemical interactions, obstacles and distribution of chemoattractant in the environment. While previous research has shown that bacterial motion is non-ergodic, we demonstrate that, besides the non-ergodicity, the bacterial swimming dynamics is multi-fractal in nature. Finally, we demonstrate that the multi-fractal characteristic of bacterial dynamics is strongly affected by bacterial density and chemoattractant concentration.

pi

link (url) DOI [BibTex]

pi Koorehdavoudi, H., Bogdan, P., Wei, G., Marculescu, R., Zhuang, J., Carlsen, R. W., Sitti, M. Multi-fractal characterization of bacterial swimming dynamics: a case study on real and simulated Serratia marcescens Proceedings of the Royal Society of London A: Mathematical, Physical and Engineering Sciences, 473(2203), The Royal Society, 2017 (article)

link (url) DOI [BibTex]

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Microemulsion-Based Soft Bacteria-Driven Microswimmers for Active Cargo Delivery

Singh, A. V., Hosseinidoust, Z., Park, B., Yasa, O., Sitti, M.

ACS Nano, 0(0):null, 2017, PMID: 28858477 (article)

Abstract
Biohybrid cell-driven microsystems offer unparalleled possibilities for realization of soft microrobots at the micron scale. Here, we introduce a bacteria-driven microswimmer that combines the active locomotion and sensing capabilities of bacteria with the desirable encapsulation and viscoelastic properties of a soft double-micelle microemulsion for active transport and delivery of cargo (e.g., imaging agents, genes, and drugs) to living cells. Quasi-monodisperse double emulsions were synthesized with an aqueous core that encapsulated the fluorescence imaging agents, as a proof-of-concept cargo in this study, and an outer oil shell that was functionalized with streptavidin for specific and stable attachment of biotin-conjugated Escherichia coli. Motile bacteria effectively propelled the soft microswimmers across a Transwell membrane, actively delivering imaging agents (i.e., dyes) encapsulated inside of the micelles to a monolayer of cultured MCF7 breast cancer and J744A.1 macrophage cells, which enabled real-time, live-cell imaging of cell organelles, namely mitochondria, endoplasmic reticulum, and Golgi body. This in vitro model demonstrates the proof-of-concept feasibility of the proposed soft microswimmers and offers promise for potential biomedical applications in active and/or targeted transport and delivery of imaging agents, drugs, stem cells, siRNA, and therapeutic genes to live tissue in in vitro disease models (e.g., organ-on-a-chip devices) and stagnant or low-flow-velocity fluidic regions of the human body.

pi

link (url) DOI Project Page [BibTex]

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Mode Evolution in Strongly Coupled Plasmonic Dolmens Fabricated by Templated Assembly

Flauraud, V., Bernasconi, G. D., Butet, J., Mastrangeli, M., Alexander, D. T. L., Martin, O. J. F., Brugger, J.

ACS Photonics, 4(7):1661-1668, 2017 (article)

Abstract
Plasmonic antennas have enabled a wealth of applications that exploit tailored near-fields and radiative properties, further endowed by the bespoke interactions of multiple resonant building blocks. Specifically, when the interparticle distances are reduced to a few nanometers, coupling may be greatly enhanced leading to ultimate near-field intensities and confinement along with a large energy splitting of resonant modes. While this concept is well-known, the fabrication and characterization of suitable multimers with controlled geometries and few-nanometer gaps remains highly challenging. In this article, we present the topographically templated assembly of single-crystal colloidal gold nanorods into trimers, with a dolmen geometry. This fabrication method enables the precise positioning of high-quality nanorods, with gaps as small as 1.5 nm, which permits a gradual and controlled symmetry breaking by tuning the arrangement of these strongly coupled nanostructures. To characterize the fabricated structures, we perform electron energy loss spectroscopy (EELS) near-field hyperspectral imaging and geometrically accurate EELS, plane wave, and eigenmode full-wave computations to reveal the principles governing the electromagnetic response of such nanostructures that have been extensively studied under plane wave excitation for their Fano resonant properties. These experiments track the evolution of the multipolar interactions with high accuracy as the antenna geometry varies. Our results provide new insights in strongly coupled single-crystal building blocks and open news opportunities for the design and fabrication of plasmonic systems.

pi

link (url) DOI [BibTex]

pi Flauraud, V., Bernasconi, G. D., Butet, J., Mastrangeli, M., Alexander, D. T. L., Martin, O. J. F., Brugger, J. Mode Evolution in Strongly Coupled Plasmonic Dolmens Fabricated by Templated Assembly ACS Photonics, 4(7):1661-1668, 2017 (article)

link (url) DOI [BibTex]

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Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery

Amjadia, M., Mostaghacia, B., Sittia, M.

Current Gene Therapy, 17, 2017 (article)

Abstract
There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs.

pi

DOI [BibTex]

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A fully dense and globally consistent 3D map reconstruction approach for GI tract to enhance therapeutic relevance of the endoscopic capsule robot

Turan, M., Pilavci, Y. Y., Jamiruddin, R., Araujo, H., Konukoglu, E., Sitti, M.

arXiv preprint arXiv:1705.06524, 2017 (article)

Abstract
In the gastrointestinal (GI) tract endoscopy field, ingestible wireless capsule endoscopy is emerging as a novel, minimally invasive diagnostic technology for inspection of the GI tract and diagnosis of a wide range of diseases and pathologies. Since the development of this technology, medical device companies and many research groups have made substantial progress in converting passive capsule endoscopes to robotic active capsule endoscopes with most of the functionality of current active flexible endoscopes. However, robotic capsule endoscopy still has some challenges. In particular, the use of such devices to generate a precise three-dimensional (3D) mapping 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 and intuitively, thus permitting more reliable diagnoses. To our knowledge, this paper presents the first complete pipeline for a complete 3D visual map reconstruction of the stomach. The proposed pipeline is modular and includes a preprocessing module, an image registration module, and a final shape-from-shading-based 3D reconstruction module; the 3D map is primarily generated by a combination of image stitching and shape-from-shading techniques, and is updated in a frame-by-frame iterative fashion via capsule motion inside the stomach. A comprehensive quantitative analysis of the proposed 3D reconstruction method is performed using an esophagus gastro duodenoscopy simulator, three different endoscopic cameras, and a 3D optical scanner.

pi

link (url) Project Page [BibTex]

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Mobile microrobots for bioengineering applications

Ceylan, H., Giltinan, J., Kozielski, K., Sitti, M.

Lab on a Chip, 17(10):1705-1724, Royal Society of Chemistry, 2017 (article)

Abstract
Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells. They are aimed to operate robustly and safely in complex physiological environments where they will have a transforming impact in bioengineering and healthcare. Research along this line has already demonstrated significant progress, increasing attention, and high promise over the past several years. The first-generation microrobots, which could deliver therapeutics and other cargo to targeted specific body sites, have just been started to be tested inside small animals toward clinical use. Here, we review frontline advances in design, fabrication, and testing of untethered mobile microrobots for bioengineering applications. We convey the most impactful and recent strategies in actuation, mobility, sensing, and other functional capabilities of mobile microrobots, and discuss their potential advantages and drawbacks to operate inside complex, enclosed and physiologically relevant environments. We lastly draw an outlook to provide directions in the veins of more sophisticated designs and applications, considering biodegradability, immunogenicity, mobility, sensing, and possible medical interventions in complex microenvironments.

pi

DOI [BibTex]

pi Ceylan, H., Giltinan, J., Kozielski, K., Sitti, M. Mobile microrobots for bioengineering applications Lab on a Chip, 17(10):1705-1724, Royal Society of Chemistry, 2017 (article)

DOI [BibTex]

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Surface tension-driven self-alignment

Mastrangeli, M., Zhou, Q., Sariola, V., Lambert, P.

Soft Matter, 13, pages: 304-327, The Royal Society of Chemistry, 2017 (article)

Abstract
Surface tension-driven self-alignment is a passive and highly-accurate positioning mechanism that can significantly simplify and enhance the construction of advanced microsystems. After years of research{,} demonstrations and developments{,} the surface engineering and manufacturing technology enabling capillary self-alignment has achieved a degree of maturity conducive to a successful transfer to industrial practice. In view of this transition{,} a broad and accessible review of the physics{,} material science and applications of capillary self-alignment is presented. Statics and dynamics of the self-aligning action of deformed liquid bridges are explained through simple models and experiments{,} and all fundamental aspects of surface patterning and conditioning{,} of choice{,} deposition and confinement of liquids{,} and of component feeding and interconnection to substrates are illustrated through relevant applications in micro- and nanotechnology. A final outline addresses remaining challenges and additional extensions envisioned to further spread the use and fully exploit the potential of the technique.

pi

link (url) DOI [BibTex]

pi Mastrangeli, M., Zhou, Q., Sariola, V., Lambert, P. Surface tension-driven self-alignment Soft Matter, 13, pages: 304-327, The Royal Society of Chemistry, 2017 (article)

link (url) DOI [BibTex]

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A Deep Learning Based 6 Degree-of-Freedom Localization Method for Endoscopic Capsule Robots

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

arXiv preprint arXiv:1705.05435, 2017 (article)

Abstract
We present a robust deep learning based 6 degrees-of-freedom (DoF) localization system for endoscopic capsule robots. Our system mainly focuses on localization of endoscopic capsule robots inside the GI tract using only visual information captured by a mono camera integrated to the robot. The proposed system is a 23-layer deep convolutional neural network (CNN) that is capable to estimate the pose of the robot in real time using a standard CPU. The dataset for the evaluation of the system was recorded inside a surgical human stomach model with realistic surface texture, softness, and surface liquid properties so that the pre-trained CNN architecture can be transferred confidently into a real endoscopic scenario. An average error of 7.1% and 3.4% for translation and rotation has been obtained, respectively. The results accomplished from the experiments demonstrate that a CNN pre-trained with raw 2D endoscopic images performs accurately inside the GI tract and is robust to various challenges posed by reflection distortions, lens imperfections, vignetting, noise, motion blur, low resolution, and lack of unique landmarks to track.

pi

link (url) Project Page [BibTex]

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Deep EndoVO: A Recurrent Convolutional Neural Network (RCNN) based Visual Odometry Approach for Endoscopic Capsule Robots

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

ArXiv e-prints, 2017 (article)

Abstract
Ingestible wireless capsule endoscopy is an emerging minimally invasive diagnostic technology for inspection of the GI tract and diagnosis of a wide range of diseases and pathologies. Medical device companies and many research groups have recently made substantial progresses in converting passive capsule endoscopes to active capsule robots, enabling more accurate, precise, and intuitive detection of the location and size of the diseased areas. Since a reliable real time pose estimation functionality is crucial for actively controlled endoscopic capsule robots, in this study, we propose a monocular visual odometry (VO) method for endoscopic capsule robot operations. Our method lies on the application of the deep Recurrent Convolutional Neural Networks (RCNNs) for the visual odometry task, where Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs) are used for the feature extraction and inference of dynamics across the frames, respectively. Detailed analyses and evaluations made on a real pig stomach dataset proves that our system achieves high translational and rotational accuracies for different types of endoscopic capsule robot trajectories.

pi

link (url) Project Page [BibTex]

2014

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Series of Multilinked Caterpillar Track-type Climbing Robots

Lee, G., Kim, H., Seo, K., Kim, J., Sitti, M., Seo, T.

Journal of Field Robotics, November 2014 (article)

Abstract
Climbing robots have been widely applied in many industries involving hard to access, dangerous, or hazardous environments to replace human workers. Climbing speed, payload capacity, the ability to overcome obstacles, and wall-to-wall transitioning are significant characteristics of climbing robots. Here, multilinked track wheel-type climbing robots are proposed to enhance these characteristics. The robots have been developed for five years in collaboration with three universities: Seoul National University, Carnegie Mellon University, and Yeungnam University. Four types of robots are presented for different applications with different surface attachment methods and mechanisms: MultiTank for indoor sites, Flexible caterpillar robot (FCR) and Combot for heavy industrial sites, and MultiTrack for high-rise buildings. The method of surface attachment is different for each robot and application, and the characteristics of the joints between links are designed as active or passive according to the requirement of a given robot. Conceptual design, practical design, and control issues of such climbing robot types are reported, and a proper choice of the attachment methods and joint type is essential for the successful multilink track wheel-type climbing robot for different surface materials, robot size, and computational costs.

pi

DOI [BibTex]

2014

pi Lee, G., Kim, H., Seo, K., Kim, J., Sitti, M., Seo, T. Series of Multilinked Caterpillar Track-type Climbing Robots Journal of Field Robotics, November 2014 (article)

DOI [BibTex]

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Segmented molecular design of self-healing proteinaceous materials.

Sariola, V., Pena-Francesch, A., Jung, H., Çetinkaya, M., Pacheco, C., Sitti, M., Demirel, M. C.

Scientific reports, 5, pages: 13482-13482, Nature Publishing Group, July 2014 (article)

Abstract
Hierarchical assembly of self-healing adhesive proteins creates strong and robust structural and interfacial materials, but understanding of the molecular design and structure–property relationships of structural proteins remains unclear. Elucidating this relationship would allow rational design of next generation genetically engineered self-healing structural proteins. Here we report a general self-healing and -assembly strategy based on a multiphase recombinant protein based material. Segmented structure of the protein shows soft glycine- and tyrosine-rich segments with self-healing capability and hard beta-sheet segments. The soft segments are strongly plasticized by water, lowering the self-healing temperature close to body temperature. The hard segments self-assemble into nanoconfined domains to reinforce the material. The healing strength scales sublinearly with contact time, which associates with diffusion and wetting of autohesion. The finding suggests that recombinant structural proteins from heterologous expression have potential as strong and repairable engineering materials.

pi

DOI [BibTex]

pi Sariola, V., Pena-Francesch, A., Jung, H., Çetinkaya, M., Pacheco, C., Sitti, M., Demirel, M. C. Segmented molecular design of self-healing proteinaceous materials. Scientific reports, 5, pages: 13482-13482, Nature Publishing Group, July 2014 (article)

DOI [BibTex]

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Bio-Hybrid Cell-Based Actuators for Microsystems

Carlsen, R. W., Sitti, M.

Small, 10(19):3831-3851, June 2014 (article)

Abstract
As we move towards the miniaturization of devices to perform tasks at the nano and microscale, it has become increasingly important to develop new methods for actuation, sensing, and control. Over the past decade, bio-hybrid methods have been investigated as a promising new approach to overcome the challenges of scaling down robotic and other functional devices. These methods integrate biological cells with artificial components and therefore, can take advantage of the intrinsic actuation and sensing functionalities of biological cells. Here, the recent advancements in bio-hybrid actuation are reviewed, and the challenges associated with the design, fabrication, and control of bio-hybrid microsystems are discussed. As a case study, focus is put on the development of bacteria-driven microswimmers, which has been investigated as a targeted drug delivery carrier. Finally, a future outlook for the development of these systems is provided. The continued integration of biological and artificial components is envisioned to enable the performance of tasks at a smaller and smaller scale in the future, leading to the parallel and distributed operation of functional systems at the microscale.

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DOI [BibTex]

pi Carlsen, R. W., Sitti, M. Bio-Hybrid Cell-Based Actuators for Microsystems Small, 10(19):3831-3851, June 2014 (article)

DOI [BibTex]

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Continuously distributed magnetization profile for millimeter-scale elastomeric undulatory swimming

Diller, E., Zhuang, J., Zhan Lum, G., Edwards, M. R., Sitti, M.

Applied Physics Letters, 104(17):174101, AIP, 2014 (article)

Abstract
We have developed a millimeter-scale magnetically driven swimming robot for untethered motion at mid to low Reynolds numbers. The robot is propelled by continuous undulatory deformation, which is enabled by the distributed magnetization profile of a flexible sheet. We demonstrate control of a prototype device and measure deformation and speed as a function of magnetic field strength and frequency. Experimental results are compared with simple magnetoelastic and fluid propulsion models. The presented mechanism provides an efficient remote actuation method at the millimeter scale that may be suitable for further scaling down in size for microrobotics applications in biotechnology and healthcare

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link (url) DOI [BibTex]

pi Diller, E., Zhuang, J., Zhan Lum, G., Edwards, M. R., Sitti, M. Continuously distributed magnetization profile for millimeter-scale elastomeric undulatory swimming Applied Physics Letters, 104(17):174101, AIP, 2014 (article)

link (url) DOI [BibTex]