Stimuli-Responsive Soft Untethered Grippers for Drug Delivery and Robotic Surgery

Untethered microtools that can be precisely navigated into deep in vivo locations are important for clinical procedures pertinent to minimally invasive surgery and targeted drug delivery. In this mini-review, untethered soft grippers are discussed, with an emphasis on a class of autonomous stimuli-responsive gripping soft tools that can be used to excise tissues and release drugs in a controlled manner. The grippers are composed of polymers and hydrogels and are thus compliant to soft tissues. They can be navigated using magnetic fields and controlled by robotic path-planning strategies to carry out tasks like pick-and-place of microspheres and biological materials either with user assistance, or in a fully autonomous manner. It is envisioned that the use of these untethered soft grippers will translate from laboratory experiments to clinical scenarios and the challenges that need to be overcome to make this transition are discussed.

[1]  Ambarish Ghosh,et al.  Conformal cytocompatible ferrite coatings facilitate the realization of a nanovoyager in human blood. , 2014, Nano letters.

[2]  Shaoyi Jiang,et al.  Zwitterionic hydrogels implanted in mice resist the foreign-body reaction , 2013, Nature Biotechnology.

[3]  Robert J. Wood,et al.  Soft Robotic Grippers for Biological Sampling on Deep Reefs , 2016, Soft robotics.

[4]  C. Majidi Soft Robotics: A Perspective—Current Trends and Prospects for the Future , 2014 .

[5]  E. Gil,et al.  Stimuli-reponsive polymers and their bioconjugates , 2004 .

[6]  Cameron Alexander,et al.  Bioadhesion at micro-patterned stimuli-responsive polymer brushes , 2005 .

[7]  Wei Gao,et al.  Functionalized ultrasound-propelled magnetically guided nanomotors: toward practical biomedical applications. , 2013, ACS nano.

[8]  Heather E Canavan,et al.  Biological cell detachment from poly(N-isopropyl acrylamide) and its applications. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[9]  B. Nelson,et al.  Microrobots: a new era in ocular drug delivery , 2014, Expert opinion on drug delivery.

[10]  S. Martel,et al.  Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions , 2016, Nature nanotechnology.

[11]  E. Smela Conjugated Polymer Actuators for Biomedical Applications , 2003 .

[12]  G. Prando,et al.  Graphene spintronics: Rashba or not Rashba? , 2016 .

[13]  MajidiCarmel,et al.  Soft Robotics: A Perspective—Current Trends and Prospects for the Future , 2014 .

[14]  Hye Rin Kwag,et al.  Stimuli-responsive theragrippers for chemomechanical controlled release. , 2014, Angewandte Chemie.

[15]  Filip Ilievski,et al.  Soft robotics for chemists. , 2011, Angewandte Chemie.

[16]  Wei Wang,et al.  Autonomous motion of metallic microrods propelled by ultrasound. , 2012, ACS nano.

[17]  D. Wiersma,et al.  Structured light enables biomimetic swimming and versatile locomotion of photoresponsive soft microrobots. , 2016, Nature materials.

[18]  Oliver G. Schmidt,et al.  Development of a Sperm‐Flagella Driven Micro‐Bio‐Robot , 2013, Advanced materials.

[19]  Hwan Chul Jeon,et al.  Controlled origami folding of hydrogel bilayers with sustained reversibility for robust microcarriers. , 2012, Angewandte Chemie.

[20]  Charles U Nottingham,et al.  The Impact of Minimally Invasive Surgery on Major Iatrogenic Ureteral Injury and Subsequent Ureteral Repair During Hysterectomy: A National Analysis of Risk Factors and Outcomes. , 2016, Urology.

[21]  ChangKyu Yoon,et al.  Control of untethered soft grippers for pick-and-place tasks , 2016, 2016 6th IEEE International Conference on Biomedical Robotics and Biomechatronics (BioRob).

[22]  J. Kjems,et al.  Self-assembly of a nanoscale DNA box with a controllable lid , 2009, Nature.

[23]  F. Qiu,et al.  Controlled In Vivo Swimming of a Swarm of Bacteria‐Like Microrobotic Flagella , 2015, Advanced materials.

[24]  P. Wells Current status and future technical advances of ultrasonic imaging , 2000, IEEE Engineering in Medicine and Biology Magazine.

[25]  Paolo Dario,et al.  Analysis and development of locomotion devices for the gastrointestinal tract , 2002, IEEE Transactions on Biomedical Engineering.

[26]  Teruo Okano,et al.  Pulsatile drug release control using hydrogels. , 2002, Advanced drug delivery reviews.

[27]  Hye Rin Kwag,et al.  Self-Folding Thermo-Magnetically Responsive Soft Microgrippers , 2015, ACS applied materials & interfaces.

[28]  M. Jamal,et al.  Enzymatically triggered actuation of miniaturized tools. , 2010, Journal of the American Chemical Society.

[29]  Nathalie Katsonis,et al.  Molecular machines: Nanomotor rotates microscale objects , 2006, Nature.

[30]  T. Nanayakkara,et al.  Soft Robotics Technologies to Address Shortcomings in Today ’ s Minimally Invasive Surgery : The STIFF-FLOP Approach , 2014 .

[31]  L. Ionov Biomimetic Hydrogel‐Based Actuating Systems , 2013 .

[32]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[33]  D. Schmaljohann Thermo- and pH-responsive polymers in drug delivery. , 2006, Advanced drug delivery reviews.

[34]  P. Fischer,et al.  Magnetic Propulsion of Microswimmers with DNA-Based Flagellar Bundles , 2016, Nano letters.

[35]  Stefano Scheggi,et al.  Autonomous planning and control of soft untethered grippers in unstructured environments , 2016, Journal of Micro-Bio Robotics.

[36]  LuNanshu,et al.  Flexible and Stretchable Electronics Paving the Way for Soft Robotics , 2014 .

[37]  R. Langer,et al.  Light-induced shape-memory polymers , 2005, Nature.

[38]  Nanshu Lu,et al.  Flexible and Stretchable Electronics Paving the Way for Soft Robotics , 2013 .

[39]  Elisabetta A. Matsumoto,et al.  Biomimetic 4D printing. , 2016, Nature materials.

[40]  B Mazzolai,et al.  Soft-robotic arm inspired by the octopus: II. From artificial requirements to innovative technological solutions , 2012, Bioinspiration & biomimetics.

[41]  Ryan R. Kohlmeyer,et al.  Wavelength-selective, IR light-driven hinges based on liquid crystalline elastomer composites. , 2013, Angewandte Chemie.

[42]  Filip Ilievski,et al.  Multigait soft robot , 2011, Proceedings of the National Academy of Sciences.

[43]  Daniela Rus,et al.  Autonomous Soft Robotic Fish Capable of Escape Maneuvers Using Fluidic Elastomer Actuators. , 2014, Soft robotics.

[44]  Hye Rin Kwag,et al.  A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma , 2016 .

[45]  J Dankelman,et al.  Scopes Too Flexible...and Too Stiff , 2010, IEEE Pulse.

[46]  Yoseph Bar-Cohen EAP History, Current Status, and Infrastructure , 2004 .

[47]  S. Martel,et al.  Automatic navigation of an untethered device in the artery of a living animal using a conventional clinical magnetic resonance imaging system , 2007 .

[48]  Claudio Pacchierotti,et al.  Evaluation of an electromagnetic system with haptic feedback for control of untethered, soft grippers affected by disturbances , 2016, 2016 6th IEEE International Conference on Biomedical Robotics and Biomechatronics (BioRob).

[49]  G. Rangarajan,et al.  Velocity Fluctuations in Helical Propulsion: How Small Can a Propeller Be. , 2014, The journal of physical chemistry letters.

[50]  Stephan Schmidt,et al.  Adhesion and Mechanical Properties of PNIPAM Microgel Films and Their Potential Use as Switchable Cell Culture Substrates , 2010 .

[51]  P. Gupta,et al.  Hydrogels: from controlled release to pH-responsive drug delivery. , 2002, Drug discovery today.

[52]  Toyoichi Tanaka,et al.  Volume phase transition in a non‐ionic gel , 1984 .

[53]  D. Castner,et al.  Biomedical surface science: Foundations to frontiers , 2002 .

[54]  Metin Sitti,et al.  Soft Grippers Using Micro‐fibrillar Adhesives for Transfer Printing , 2014, Advanced materials.

[55]  Shoji Maruo,et al.  Three-dimensional microfabrication with two-photon absorbed photopolymerization , 1996, International Commission for Optics.

[56]  A. Kalloo,et al.  Biopsy with Thermally‐Responsive Untethered Microtools , 2013, Advanced materials.

[57]  D. Floreano,et al.  Versatile Soft Grippers with Intrinsic Electroadhesion Based on Multifunctional Polymer Actuators , 2016, Advanced materials.

[58]  Claudio Pacchierotti,et al.  Steering and Control of Miniaturized Untethered Soft Magnetic Grippers With Haptic Assistance , 2018, IEEE Transactions on Automation Science and Engineering.

[59]  Ambarish Ghosh,et al.  Dynamical configurations and bistability of helical nanostructures under external torque. , 2012, Physical review. E, Statistical, nonlinear, and soft matter physics.

[60]  Adam Heller,et al.  Bioelectrochemical propulsion. , 2005, Journal of the American Chemical Society.

[61]  Jiachen Zhang,et al.  Reliable Grasping of Three-Dimensional Untethered Mobile Magnetic Microgripper for Autonomous Pick-and-Place , 2017, IEEE Robotics and Automation Letters.

[62]  Huai-Ti Lin,et al.  GoQBot: a caterpillar-inspired soft-bodied rolling robot , 2011, Bioinspiration & biomimetics.

[63]  Miklós Zrínyi,et al.  Ferrogel: a new magneto-controlled elastic medium , 1997 .

[64]  Salvador Pané,et al.  Soft micromachines with programmable motility and morphology , 2016, Nature Communications.

[65]  C. Keplinger,et al.  25th Anniversary Article: A Soft Future: From Robots and Sensor Skin to Energy Harvesters , 2013, Advanced materials.

[66]  R. Pfeifer,et al.  Self-Organization, Embodiment, and Biologically Inspired Robotics , 2007, Science.

[67]  Leonid Ionov,et al.  Soft microorigami: self-folding polymer films , 2011 .

[68]  D. Gracias Stimuli responsive self-folding using thin polymer films , 2013 .

[69]  Oliver Brock,et al.  A novel type of compliant and underactuated robotic hand for dexterous grasping , 2016, Int. J. Robotics Res..

[70]  R. Cerfolio,et al.  Incidence, Results, and Our Current Intraoperative Technique to Control Major Vascular Injuries During Minimally Invasive Robotic Thoracic Surgery. , 2016, The Annals of thoracic surgery.

[71]  D W Hutmacher,et al.  An introduction to biodegradable materials for tissue engineering applications. , 2001, Annals of the Academy of Medicine, Singapore.

[72]  Robert J. Wood,et al.  Peristaltic locomotion with antagonistic actuators in soft robotics , 2010, 2010 IEEE International Conference on Robotics and Automation.

[73]  B Gleich,et al.  Three-dimensional real-time in vivo magnetic particle imaging , 2009, Physics in medicine and biology.

[74]  Lixin Dong,et al.  Artificial bacterial flagella: Fabrication and magnetic control , 2009 .

[75]  J. Bodle,et al.  High-Resolution Magnetic Resonance Imaging: An Emerging Tool for Evaluating Intracranial Arterial Disease , 2013, Stroke.

[76]  David S. Jones,et al.  Mucoadhesive polymeric platforms for controlled drug delivery. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[77]  Leon Abelmann,et al.  Closed-loop control of magnetotactic bacteria , 2013, Int. J. Robotics Res..

[78]  Angelo S. Mao,et al.  An Integrated Microrobotic Platform for On‐Demand, Targeted Therapeutic Interventions , 2014, Advanced materials.

[79]  P. Fischer,et al.  Controlled propulsion of artificial magnetic nanostructured propellers. , 2009, Nano letters.

[80]  Jamie L. Branch,et al.  Robotic Tentacles with Three‐Dimensional Mobility Based on Flexible Elastomers , 2013, Advanced materials.

[81]  L. J. Lee,et al.  Self-folding of three-dimensional hydrogel microstructures. , 2005, The journal of physical chemistry. B.

[82]  W. Chitwood,et al.  Evolution of mitral valve surgery: toward a totally endoscopic approach. , 2001, The Annals of thoracic surgery.

[83]  Daniela Rus,et al.  Ingestible, controllable, and degradable origami robot for patching stomach wounds , 2016, 2016 IEEE International Conference on Robotics and Automation (ICRA).

[84]  D. W. Pack,et al.  Uniform biodegradable microparticle systems for controlled release , 2015 .

[85]  Blake Hannaford,et al.  Measurement and modeling of McKibben pneumatic artificial muscles , 1996, IEEE Trans. Robotics Autom..

[86]  Robert Langer,et al.  Perspective: Special delivery for the gut , 2015, Nature.

[87]  Yanyan Cao,et al.  Catalytic nanomotors: autonomous movement of striped nanorods. , 2004, Journal of the American Chemical Society.

[88]  Franziska Ullrich,et al.  Magnetically actuated and guided milli-gripper for medical applications , 2015, 2015 IEEE International Conference on Robotics and Automation (ICRA).

[89]  Stefano Scheggi,et al.  Magnetic motion control and planning of untethered soft grippers using ultrasound image feedback , 2017, 2017 IEEE International Conference on Robotics and Automation (ICRA).

[90]  Kyu-Jin Cho,et al.  Omega-Shaped Inchworm-Inspired Crawling Robot With Large-Index-and-Pitch (LIP) SMA Spring Actuators , 2013, IEEE/ASME Transactions on Mechatronics.

[91]  Ioannis K. Kaliakatsos,et al.  Microrobots for minimally invasive medicine. , 2010, Annual review of biomedical engineering.

[92]  Frederik L. Giesel,et al.  3D printing based on imaging data: review of medical applications , 2010, International Journal of Computer Assisted Radiology and Surgery.

[93]  Nikolaus Correll,et al.  Materials that couple sensing, actuation, computation, and communication , 2015, Science.

[94]  G. Dogangil,et al.  A review of medical robotics for minimally invasive soft tissue surgery , 2010, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[95]  Jong-Oh Park,et al.  Magnetic actuated pH-responsive hydrogel-based soft micro-robot for targeted drug delivery , 2016 .

[96]  Zhibing Hu,et al.  Synthesis and Application of Modulated Polymer Gels , 1995, Science.

[97]  Heinrich M. Jaeger,et al.  Universal robotic gripper based on the jamming of granular material , 2010, Proceedings of the National Academy of Sciences.

[98]  M. Sitti,et al.  Three‐Dimensional Programmable Assembly by Untethered Magnetic Robotic Micro‐Grippers , 2014 .

[99]  A. Lendlein,et al.  Shape-memory polymers as a technology platform for biomedical applications , 2010, Expert review of medical devices.

[100]  Fumiya Iida,et al.  Soft Manipulators and Grippers: A Review , 2016, Front. Robot. AI.

[101]  CianchettiMatteo,et al.  Soft Robotics Technologies to Address Shortcomings in Today's Minimally Invasive Surgery: The STIFF-FLOP Approach , 2014 .

[102]  Andrew G. Gillies,et al.  Optically-and Thermally-responsive Programmable Materials Based on Carbon Nanotube-hydrogel Polymer Composites , 2022 .

[103]  J. Frangioni In vivo near-infrared fluorescence imaging. , 2003, Current opinion in chemical biology.

[104]  C. Alexander,et al.  Stimuli responsive polymers for biomedical applications. , 2005, Chemical Society reviews.

[105]  Eric Diller,et al.  Biomedical Applications of Untethered Mobile Milli/Microrobots , 2015, Proceedings of the IEEE.

[106]  D. Rus,et al.  Design, fabrication and control of soft robots , 2015, Nature.

[107]  R. Langer,et al.  Biodegradable, Elastic Shape-Memory Polymers for Potential Biomedical Applications , 2002, Science.

[108]  Sirilak Sattayasamitsathit,et al.  Propulsion of nanowire diodes. , 2010, Chemical communications.

[109]  Peter R Luijten,et al.  In Vivo Detection of Cerebral Cortical Microinfarcts with High-Resolution 7T MRI , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[110]  S. Martel,et al.  Magnetic nanoparticles encapsulated into biodegradable microparticles steered with an upgraded magnetic resonance imaging system for tumor chemoembolization. , 2009, Biomaterials.

[111]  Robert J. Wood,et al.  Soft robotic glove for combined assistance and at-home rehabilitation , 2015, Robotics Auton. Syst..

[112]  R. Adhikari,et al.  Biodegradable synthetic polymers for tissue engineering. , 2003, European cells & materials.

[113]  M. Chen,et al.  Interventional Management of Intracranial Stenosis , 2010, The Open Atherosclerosis & Thrombosis Journal.

[114]  H. G. Schild Poly(N-isopropylacrylamide): experiment, theory and application , 1992 .

[115]  J. O. Simpson,et al.  Ionic polymer-metal composites (IPMCs) as biomimetic sensors, actuators and artificial muscles - a review , 1998 .