Donglei (Emma) Fan, University of Texas at Austin
Xiaodong Chen, Nanyang Technological University
Peer Fischer, Max Planck Institute for Intelligent Systems
Tony Huang, Duke University
NM10.1: Nanomanipulation and Nanomotors I
Donglei (Emma) Fan
Tuesday PM, April 18, 2017
PCC West, 100 Level, Room 102 AB
11:30 AM - *NM10.1.01
3D Printed Skeletal Muscle-Powered Biological Machines
Rashid Bashir 1 2 , Ritu Raman 2 3 , Caroline Cvetkovic 1 2 , Lauren Grant 1 2 Show Abstract
1 Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, 2 , Micro and Nanotechnology Laboratory, Urbana, Illinois, United States, 3 Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
Biological materials can dynamically sense and adaptively respond to changing environmental signals in real-time. This gives them the ability to self assemble, self organize, self heal, self replicate, and generally demonstrate higher-level functional behaviors than capable with synthetic materials. These capabilities motivate the use of biological materials in reverse engineering native tissue for applications in regenerative medicine, an also forward engineering bio-integrated machines for a range of functional applications.
Manufacturing complex 3D structures using biological materials requires an enabling technology, such as 3D printing. Recent advances in our lab have demonstrated a variety of stereolithographic 3D printing approaches to efficiently pattern cells and cell signals at the macro- and micro- scale1,2. Using these apparatus, we have reverse engineered tissue and organs in vitro to develop a better understanding of biological systems in vivo and develop replacements for diseased or damaged tissue.
We have also 3D printed flexible soft-robotic skeletons powered by tissue engineered skeletal muscle and controlled by electrical and optical signals3,4. To demonstrate the power of skeletal muscle as a complex controllable bioactuator, we have optimized the manufacture of modular and robust muscle-powered robots (bio-bots) that can, in future, be targeted at an array of grand engineering challenges5.
This work was sponsored by the NSF Emergent Behavior of Integrated Cellular Systems (EBICS) STC under Grant CBET-0939511.
 Chan et al, Lab on a Chip (2010).
 Raman et al, Advanced Healthcare Materials (2015).
 Cvetkovic & Raman, et al, PNAS (2014).
 Raman et al, PNAS (2016).
 Raman et al, Nature Protocols (2016).
12:30 PM - NM10.1.03
Highly Efficient Light-Driven Micro/Nanomotors
Wei Gao 1 , Renfeng Dong 2 , Zhiguang Wu 3 , Joseph Wang 4 Show Abstract
1 , University of California, Berkeley, Berkeley, California, United States, 2 , South China University of Technology, Guangzhou China, 3 , Harbin Institute of Technology, Harbin China, 4 , University of California, San Diego, La Jolla, California, United States
The propulsion of micro/nanoscale objects holds great promises for numerous applications including drug delivery, precision surgery and environmental remediation. Fuel-free micro/nanomachines, powered by various external stimuli such as light, magnetic, electrical and ultrasound fields, are particularly attractive owing to their great biocompatibility. As one of the most versatile physical stimuli, light can be used to realize and regulate the propulsion of synthetic micro/nanomotors. A photocatalytic TiO2–Au Janus nanomotor is developed which displays efficient propulsion in pure water under UV light. Unlike chemically propelled motors which commonly require the addition of surfactants or toxic chemical fuels, this fuel-free Janus nanomotor can be powered under an extremely low ultraviolet light intensity at a speed comparable to common Pt-based catalytic nanomotors. Such photocatalytic propulsion can be switched on and off by incident light modulation and the speed of TiO2–Au Janus micromotor can be greatly accelerated by increasing the light intensity. In addition, a gold nanoshell-functionalized NIR light driven nanorocket is presented. Theoretical simulations reveal that the NIR light-triggered self-thermophoresis drives the propulsion of the nanorocket. The nanorocket displays efficient NIR light-triggered propulsion in biofluids and is shown to be able to perform photothermal cancer therapy in cell medium. The attractive fuel-free propulsion performance and precise motion control of the light driven micromotors make them an ideal candidate for diverse practical applications.
12:45 PM - NM10.1.04
Design and Characterization of Mechanical Traps for Single Cell Capture and Analysis
Qianru Jin 1 , David Gracias 1 Show Abstract
1 Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States
The capture and real-time biochemical sensing of single cells has been a significant challenge but one that could provide significant information related to the heterogeneity of tissue samples of relevance to the diagnosis and treatment of a range of diseases.
We describe a self-folding approach in the form of single cell traps that can be used to capture single fibroblast cell and red blood cells . The highlight of this approach is that the energy required for gripping actuation was derived from bilayer stress release in biocompatible silicon monoxide and silicon dioxide thin films, requiring no wiring, tethers or batteries. Hence, the approach could be implemented either on chip in a large array or in a fluid environment for precise manipulation.
Here, we demonstrate that these traps can not only be used for capture but also analysis of with a range of modalities including surface enhanced Raman spectroscopy [2-3]. Furthermore, we also show the potential of profiling the cellular surface in 3D and high spatial resolution of different cellular components in a label free manner. In addition to Raman spectroscopy, we also highlight the use of these mechanical traps for optical sensing, force application and active trapping, which suggests that this platform provides significant capabilities for single cell manipulation and biochemical analysis.
 Malachowski K, Jamal M, Jin Q, Polat B, Morris CJ, Gracias DH, Nano Lett. 2014, 14 (7), 4164-4170.
 Li M, Kang JW, Dasari RR, Barman I., Shedding light on extinction-enhancement duality in gold nanostar-enhanced Raman spectroscopy, Angew. Chem. Int. Ed., 2014, 126(51), 14339-14343.
 Jin Q, Li M, Polat B, Paidi SK, Dai A, Zhang A, Padaguan J, Barman I, Gracias DH, Mechanical trap surface enhanced Raman spectroscopy (MTSERS) for 3D surface molecular imaging of single live cells (2016) in submission.
NM10.2: Nanomanipulation and Nanomotors II
Donglei (Emma) Fan
Tuesday PM, April 18, 2017
PCC West, 100 Level, Room 102 AB
2:30 PM - *NM10.2.01
Emergent Biological Machines from Self-Assembled Tissues Undergoing Phase Transitions
Onur Aydin 1 , Taher Saif 1 , Mohamed Elhebeary 1 Show Abstract
1 , University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
For the last few decades, engineering has produced marvelous machines and devices. However, these machines have two major limitations: they cannot self-assemble, or self-heal. With the increasing understanding of living cells, there are possibilities of developing living biological machines that may emerge from interactions between cells and between cells and engineered scaffolds. A fundamental question related to these new paradigm is the nature of interaction between the cells, and how order may emerge from randomness from such interactions, i.e., are phase transitions necessary for the evolution of living machines. Towards understanding these questions, we explored an engineered micro scale swimmer that emerges from plating of cardiomyocytes on a flexible string. Here, cardiomyocytes interact with each other and the deformable string, as they beat individually. Within 2 days of plating, the cells synchronize their dynamics and they all beat with the same frequency with no phase lag, i.e., they collectively behave as a single actuator. This collective and synchronized beating allows the string to swim in the media, mimicking a flagellum. In order to develop swimmers using muscle cells (C2C12), instead of primary cardiomyocytes, we designed and fabricated two parallel deformable strings from PDMS. The cells were than plated on the pair of strings in collagen-matrigel gel. We hypothesized that the cells will form myotubes around the strings that can be actuated for swimming. We observed that the cells first compact the gel and form a strip around the strings. The strip differentiates to myotube. However, the compaction of the gel appeared to be a strong function of cell density. In order to gain insight into the origin of cell density dependence, we formed muscle strips by plating C2C12 cells, mixed with an ECM solution of collagen and matrigel, in microfabricated wells. Typically, following polymerization, the ECM gel is compacted and remodeled by cells. We found that compaction is cell density dependent, and does not happen below a certain density. This finding allows us to investigate and quantify tissue compaction as an emergent phenomenon. Emergence occurs in complex systems with large number of degrees of freedom due to the tightly coupled interactions between the constituents, and typically manifests itself in the form of critical point transitions. To quantify the observed transition in tissue compaction in terms of the interactions between cells and the ECM, we looked at the effect of average cell-to-cell distance, x0. Plotting gel area over time for samples with different x0 reveals a cell density dependence. An analysis of the rate and extent of compaction with samples of varying x0 reveals that a transition from a ‘no-compaction’ to compaction state occurs at around 100µm. The finding points to critical interaction distance between cells necessary for tissue morphogenesis in engineered biological machines.
3:00 PM - NM10.2.02
Biohybrid Bacteria-Driven Microswimmers with Polyelectrolyte Multilayer for Targeted Drug Delivery Applications
Byung-Wook Park 1 , Oncay Yasa 1 , Jiang Zhuang 1 2 , Metin Sitti 1 2 Show Abstract
1 Physical Intelligence Department, Max Planck Institute for Intelligent Systems, Stuttgart Germany, 2 Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
A new type of biohybrid bacteria-driven microswimmers is developed as a targeted therapeutic strategy combining doxorubicin (DOX)-loaded polyelectrolyte multilayer (PEM) microcarriers with Escherichia coli bacteria. In particular, PEM layer-by-layer (LbL) technique is applied to tune physico-chemical properties for bacterial adhesion, which would be important parameters during biohybridization process. We characterize a motility of the bacteria-driven microswimmers in 3D using digital holographic micsoscopy (DHM), where the bacteria-driven microswimmers show mean speed (19.9 ± 2.4 μm/s). Magnetic nanoparticles (MNP) are encapsulated in the shell of the PEM microcarriers, in order to perform magnetic steering control that can decrease the stochastic motion of the microswimmers. The microswimmers can be controlled using magnetic field and chemical gradient, showing the enhanced directionality of the microswimmers with 2D mean speed at 10.4 ± 2.3 μm/s and 13.3 ± 4.4 μm/s, respectively. Further, a microfluidic chamber is designed for in-vitro study and the microswimmers are magnetically guided toward breast cancer cells (4T1) in the chamber. The present study suggests that the developed bacteria-dirven microswimmers incorporated with the PEM-MNP-DOX microcarriers can be used as advanced cancer targeting systems.
3:15 PM - *NM10.2.03
Tracking Particles In, On and Around Devices at the Nanoscale
Samuel Stavis 1 Show Abstract
1 , National Institute of Standards and Technology, Gaithersburg, Maryland, United States
Microscopy, particles, and devices are three topics of increasing importance in nanoscale science, technology, and commerce. The Nobel Prize in Chemistry 2014 was awarded for bringing light microscopy into the nanoscale. A variety of related methods are impacting measurements in biology, materials, and engineering. Nanoscale particles have vast potential for commercial development. Bottom-up synthesis, however, often requires the purification and characterization of products before application. Nanofabricated and microfabricated devices are enabling technologies, engineered to impose top-down control over nanoscale structure, motion, and function. Ideally, such devices are mass-produced for zero marginal cost and perform with perfect reliability. In this seminar, I will describe our recent work at the intersection of these three topics to solve related problems in the manufacturing and healthcare sectors of the national nanotechnology enterprise. I will focus on our use of optical microscopy to track nanoscale particles in, on, and around nanofabricated devices. In this way, we characterize the particles and test the devices.
4:00 PM - NM10.2.04
Emergence of Life-Like Properties from Dissipative Self-Assembly of Nanoparticles
Serim Ilday 1 , Ghaith Makey 1 , Gursoy Akguc 1 , Ozgun Yavuz 1 , Onur Tokel 1 , Ihor Pavlov 1 , Oguz Gulseren 1 , Omer Ilday 1 Show Abstract
1 , Bilkent University, Ankara Turkey
A profoundly fundamental question at the interface between physics and biology remains open: What are the minimum requirements for emergence of life-like properties from non-living systems? Life-like properties have been demonstrated, albeit never collectively, in various microscopic systems. These demonstrations were limited by slow kinetics and reliance on complex or material-specific interactions for self-assembly. Here, we report far-from-equilibrium self-assembly of colloidal nanoparticles with fast kinetics that exhibits a large variety of life-like properties, namely, autocatalysis and self-regulation, competition and self-replication, adaptation and self-healing, and motility, in a system designed to be as plain as possible: We do not use functionalised particles or commonly employed interaction mechanisms, such as optical trapping, tweezing, chemical or magnetic interactions. Instead, we exploit strong Brownian motion of the nanoparticles as a source of fluctuations and use an ultrafast laser to create spatiotemporal temperature gradients, which induce Marangoni-type microfluidic flow that drags the particles. Brownian motion and Marangoni flow lead to intricately coupled nonlinear feedback mechanisms: (i) An autocatalytic process between the fluid flow and self-assembled particle aggregates and (ii) a reaction-diffusion process between the flow, which helps form and reinforce the aggregate, and opposing Brownian motion, which regulates aggregation, while increasing the bifurcation possibilities. Although precise conditions required for emergence of life-like properties continues to be an open question, our results highlight the importance of the interplay of nonlinearity, fluctuations and feedback mechanisms in demonstrating a broad spectrum of life-like properties.
4:15 PM - NM10.2.05
Assembling and Actuation of Biomaterial-Based Micromachines and Their Applications
Kwanoh Kim 1 2 , Jianhe Guo 3 , Zexi Liang 3 , Minliang Liu 3 4 , Donglei (Emma) Fan 1 3 Show Abstract
1 Department of Mechanical Engineering, The University of Texas at Austin, Austin, Texas, United States, 2 Department of Nano Manufacturing Technology, Korea Institute of Machinery and Materials (present location), Daejeon Korea (the Republic of), 3 Materials Science and Engineering Program, The University of Texas at Austin, Austin, Texas, United States, 4 School of Mechanical Engineering, Georgia Institute of Technology (present location), Atlanta, Georgia, United States
In this work, we developed a rotary bio-micromachines using diatom frustules as integrated active components and demonstrated its applications in microfluidics and biomolecular adsorption and detection. Frustules are porous cell walls of diatoms made of silica. They are remarkably abundant in nature, highly biocompatible, and have unique ordered nanostructures on their surface. Our micromotors are comprised of diatom frustules and patterned micromagnets serving as rotors and bearings respectively. They are facilely manipulated and assembled into working devices in electric fields. They can be integrated into ordered arrays and rotated with the controlled direction and speed up to ~3000 rpm, which is one of the fastest biomaterial-based rotary micromotors. By exploiting the distinct electro-mechanical properties of diatom frustules and metallic nanowires, we obtained the first reconfigurable micro/nanomotor arrays each of which can be controlled individually. Finally, two promising applications of the diatom frustule micromachines are demonstrated: firstly, the diatom frustule micromotors are successfully assembled in microfluidic channels, and they work as microfluidic mixers and pumps; secondly, tunable adsorption of DNA onto the diatom frustule is realized by mechanical rotations and monitored in real time from micromotors functionalized with surface-enhanced Raman scattering (SERS)-active nanoparticles. This work could present an important advance in low-cost and bio-micro/nanoelectromechanical systems (bio-MEMS/NEMS) and their applications in microfluidics, biochemical sensing and delivery.
4:30 PM - NM10.2.06
Swimming Strategies of Nanowire-Based Swimmers in Newtonian Fluids
Bumjin Jang 1 , Bradley Nelson 1 , Salvador Pane i Vidal 1 , George Chatzipirpiridis 1 Show Abstract
1 Institute of Robotics and Intelligent Systems, ETHZ, Zürich Switzerland
Nanowires (NWs) are versatile one-dimensional nanostructures currently being exploited in many areas of research and technology. These architectures can be manufactured in several sizes, materials and forms (segmented, core-shell, hinged, or even more complex assemblies)1 to meet specific properties for further uses.2 NWs have also played a crucial role in the development and further miniaturization of small-scale swimmers. These tiny devices are proposed for several tasks such as targeted drug delivery, sensing, environmental remediation or cargo transport. Several NW-based swimmer designs have been proposed in the literature. These swimmers can be propelled by harvesting fuel from the environment, or steered by means of an external energy source such as magnetic or acoustic fields or combinations thereof.3 However, further development of multifunctional NW-based swimmers must adopt robust and advanced manufacturing approaches to incorporate additional components to NW platforms.
In this work, we will show new nanowire-based swimmers developed in our laboratory by exploiting template-assisted manufacturing techniques4. First, several magnetically driven swimmers will be presented and their motion characteristics will be rationalized as a function of their design and material. Several types of propulsion such as undulatory, corkscrew and rolling motion will be demonstrated. Second, we will show a new type of catalytic nanomachine based on a core-shell design and fabricated out of different materials. Our study on these nanoswimmers shows that these tiny devices are not propelled by means of a single mechanism, but rather by a combination of several ones. Additionally, we will show that our designs enable additional functionalities without compromising the motion mechanisms or limiting their applicability.
(1) Ozel, T.; Bourret, G. R.; Mirkin, C. A. Nat. Nanotechnol. 2015, 10, 319.
(2) Xia, Y.; Yang, P.; Sun, Y.; Wu, Y.; Mayers, B.; Gates, B.; Yin, Y.; Kim, F.; Yan, H. Adv. Mater. 2003, 15, 353.
(3) Wang, H.; Pumera, M. Chem. Rev. 2015, 115, 8704.
(4) Zeeshan, M. A.; Pané, S.; Youn, S. K.; Pellicer, E.; Schuerle, S.; Sort, J.; Fusco, S.; Lindo, A. M.; Park, H. G.; Nelson, B. J. Adv. Funct. Mater. 2013, 23, 823.
4:45 PM - *NM10.2.07
Enzyme Powered Nanobots as Active and Controllable Nanovehicles
Samuel Sanchez 2 1 3 Show Abstract
2 Smart Nanobiodevices, Institute for Bioengineering of Catalonia, Barcelona Spain, 1 , Max-Planck-Institute for Intelligent Systems, Stuttgart Germany, 3 , Catalan Institute for Research and Advanced Studies, Barcelona Spain
Engineering tiny bots that can be applied in life science is opening many avenues in fields such as robotics, biosensing, nanomedicine, on-chip microfluidics and more . One example could be the active and direct transport of drugs to specific locations enabled by hybrid micro-nano-bots, which are powered by highly efficient enzymatic catalytic reactions. 
Here, I will present our recent developments in the field of bio- and nano-engineering systems that can be autonomously swim and perform complex tasks. We fabricate nano-bots from mesoporous silica nanoparticles , microcapsules, and nanotubes . Our types of hybrid Nano-bots combine the best from the two worlds, biology and nanotechnology providing remote control with biocompatible fuels. We recently demonstrated the motion of nanomotors in glucose and urea fuel, overcoming the limitations of former systems where toxic fuels were employed. Current results are devoted into the internalization of nanomotors into living cells and their motion in complex media.
 S. Sanchez, Ll. Soler and J. Katuri. Angew.Chem.Int.Edit. 2015, 54,1414-1444
 X. Ma, A. C. Hortelao, T. Patiño, S. Sanchez. ACS Nano 2016 DOI: 10.1021/acsnano.6b04108
 X. Ma, A. Jannasch, U-R Albrecht, K. Hahn, A. Miguel López, E. Schäffer and S. Sanchez. Nano Lett. 2015, 15, 7043–7050.
 X. Ma, X. Wang, K. Hahn, S. Sanchez. ACS Nano. 2016, 10, 3597–3605
 X. Ma, A. C. Hortelao, A. Miguel-López and S. Sánchez. J. Am.Chem.Soc. 2016 DOI: 10.1021/jacs.6b06857
5:15 PM - NM10.2.08
Double-Powered Nanobots with Magnetotactic Behavior
Philipp Schattling 1 , Miguel Ramos-Docampo 2 , Veronica Salgueirino 2 , Brigitte Stadler 1 Show Abstract
1 Interdisciplinary Nanoscience Center, Aarhus University, Aarhus Denmark, 2 Departamento de Física Aplicada, Universidade de Vigo, Vigo Spain
The success of nanomachines can be explained by the auspicious range of applications nano-robots are envisioned to be used for. In particular in a biomedical context, self-propelled swimmers hold great promise to autonomously navigate to a desired location in an attempt to counteract cell/tissue defects either by releasing drugs or performing surgical tasks.
However, a variety of long-standing challenges need to be overcome before nanomachines might be translated into a biomedical context. Among those challenges are the search for and utilization of both fuels, which are biocompatible and functionalities, which allow the swimmer to be remote controlled. These important aspects are the missing pieces in the puzzle, which will allow nanomachines to be translated into a biomedical context and will let the frequently invoked vision of the Fantastic Voyage come true.
Here, we present the design of biocompatible double-fueled submicrometer sized Janus-architectures with remote control. We chose enzymatic moieties as engines and showed enhanced diffusion properties of the assemblies upon exposure to the corresponding fuel molecules. Further, we present the first biohybrid motor based on the enzyme glucose oxidase and platinum nanoparticles and a novel protein-driven motor powered by trypsin. We demonstrate that both engines were operating using bioavailable and completely harmless fuel molecules. Both motors exhibited enhanced diffusion properties, which were even exceeding our previous enzyme-swimmers by over 100%. (Chem. Mater., 2015, 27, 7412-7418) Based on their orthogonal enzymatic activity, we show for the very first time, how particles employ two different engines, using two different fuels. That is, enhanced diffusion properties were maintained even when the supply of one fuel species was disrupted. We illustrate that the swimmers exhibited a synergistic enhancement on their diffusion properties upon powering-up both engines simultaneously. We also show that the incorporation of magnetic particles allowed for the swimmer to be controlled remotely by applying an external magnetic field, yielding in directional motion of the double-fueled particles.
We believe that the intriguing concept of multiple fueled rockets is an important step towards the design of therapeutic swimmers, capable of exhibiting self-propulsion in different environmental.
5:30 PM - NM10.2.09
Structure Simplification and Motion Control of Micro/Nanomotors
Fangzhi Mou 1 , Zhen Wu 1 , Chuanrui Chen 1 , Deng Pan 1 , Yan Li 1 , Leilei Xu 1 , Jianguo Guan 1 Show Abstract
1 , Wuhan University of Technology, Wuhan China
Self-propelled micro/nanomotors (MNMs) can convert various energy into their autonomous motions, and thus have fascinating capabilities to perform complex tasks, including drug delivery, environmental remediation and micro/nanoengineering etc.1 The key principle to design self-propelled MNMs is to construct an asymmetric field across micro/nanoparticles.2-8 Following this clue, early design of MNMs to construct asymmetric fields for their propulsion depended highly on the complex Janus structures and multilayer-tubular structures, which usually need to be fabricated by complicated and expensive processing techniques, including the “rolled-up”, vapor deposition, and electrodeposition methods. In this presentation, we will demonstrate our latest works on simplifying the structure of micro/nanomotors. At first, we will present the design and large-scale preparation strategies of the single-layer structured TiO2 tubular and MnFe2O4 pot-like micromotors, which both have shape anisotropy. They exhibit controlled motion state and speed by employing the different nucleation and growth behaviors of bubbles in the confined inner spaces compared to those on the outer surfaces. Secondly, we are to introduce the basic design principles of isotropic micro/nanomotors by employing the light-induced asymmetric photocatalytic reactions owing to the limited light penetration depth in the isotropic photoresponsive particles (isotropic TiO2, Ag3PO4, ZnO and CdS particles). This can be considered as a remarkable breakthrough in design strategy of micro/nanomotors due to the simple isotropic structure of the motor and the integrated controllability in motion direction and speed by light. Last, we will demonstrate the applications of these simple-structured micromotors in oil remediation and particle manipulation. Our finding in these works may inspire novel design and the practical applications of the future micro/nanomotors due to their simple structures, as well as the facile, low cost, large-scale fabrication approaches.
 Sánchez S. Soler L. Katuri J. Angew. Chem. Int. Ed. 2015, 54, 1414-1444.
 Chen C. Mou F. Xu L. Wang S. Guan J. Feng Z. Wang Q. Kong L. Li W. Wang J. Zhang Q. Adv. Mater. 2016, DOI: 10.1002/adma.201603374.
 Mou F. Kong L. Chen C. Chen Z. Xu L., Guan J. Nanoscale 2016, 8, 4976-4983.
 Li Y. Mou F. Chen C. You M. Yin Y. Xu L., Guan J. RSC Adv. 2016, 6, 10697-10703.
 Mou F. Pan D. Chen C. Gao Y. Xu L., Guan J. Adv. Funct. Mater. 2015, 25, 6173-6181.
 Mou F. Li Y. Chen C. Li W. Yin Y. Ma H., Guan J. Small 2015, 11, 2564-2570.
 Mou F. Chen C. Zhong Q. Yin Y. Ma H., Guan J. ACS Appl. Mater. Interfaces 2014, 6, 9897-9903.
 Mou F. Chen C. Ma H. Yin Y. Wu Q. Guan J. Angew. Chem. Int. Ed. 2013, 52, 7208-7212.
5:45 PM - NM10.2.10
Shape-Transformable Liquid Metal Nanoparticles
Yiliang Lin 1 , Yue Lu 2 , Zhen Gu 2 , Jan Genzer 1 , Michael Dickey 1 Show Abstract
1 , North Carolina State University, Raleigh, North Carolina, United States, 2 , University of North Carolina at Chapel Hill, Chapel-Hill, North Carolina, United States
Metallic nanomaterials are useful as catalysts, sensors, and therapeutics. This talk focuses on the morphological control and potential applications of liquid metal nanomaterials for drug delivery utilizing eutectic gallium indium (EGaIn) (m.p. ~15.5°C). Due to its low toxicity and soft nature, we successfully produce liquid metal nanomedicine, which has the capability to fuse to fasten the drug releasing and subsequently degrade in acidic endosomes.
Here, we report the transformation of the EGaIn nanomaterials from spherical to rod-like by varying the temperature and surfactants, including proteins, at the surface of the particles. Interestingly, indium dealloys from the EGaIn while the liquid metal nanoparticles convert into nanorods. The transformation mechanism is investigated utilizing high-resolution transmission electron microscopy with chemical imaging. The soft nature of liquid metals endows the EGaIn nanomaterials with unique mechanical properties, such as deformability, and the shape-changing properties have potential applications in catalysis, optics, and drug delivery.
NM10.3: Poster Session I: Nanoparticles—Motorization
Wednesday AM, April 19, 2017
Sheraton, Third Level, Phoenix Ballroom
9:00 PM - NM10.3.01
Ultrasound Activated Film for Biomedical Imaging
Jian Yang 1 , James Wang 1 , Erin Ward 1 , Tsai Sung 1 , Christopher Barback 1 , Natalie Mendez 1 , Sarah Blair 1 , William Trogler 1 , Andrew Kummel 1 Show Abstract
1 , University of California, San Diego, La Jolla, California, United States
Bio-imaging of medical devices or surgical retain items in human body is always a challenge. We developed an ultrasound responsive thin film which could be attached to the surface of diversity materials such metal, plastic and glass. The film contains silica hollow shells and poly(cyanoacrylate) matrix. The polymer cross links the particles and bonds the film on medical devices such as surgical tools, medical catheters and other artificial implants. The polymer also blocks the pores in silica shells and keeps air in the hollow space as ultrasound contrast agent. Electric microscope found a domain of polymer and a domain mainly containing hollow shells in the film which indicates a macrophase separation happens during the polymerization. This ultrasound activated film gives strong color Doppler signals with widely used clinic ultrasound equipment. Devices coated with the film can be easily identified in human tissues and organs. The ultrasound signals have good persistence which means they can be located after several hours in tissues.
This technology provides a safe, low cost and fast method to locate the biomedical devices in vivo compared to other detection methods such as X-ray, MRI and CT. It has potential applications on small medical device tracking, biopsy marker locating, accurate needles placement and other implantable medical devices identification.
9:00 PM - NM10.3.02
Coordination-Induced Assembly of Intelligent Polysaccharide-Based Phototherapeutic Nanoparticles for Cancer Treatment
Ye Tian 1 2 , Wuli Yang 1 2 Show Abstract
1 Macromolecular Science, Fudan University, Shanghai China, 2 , State Key Laboratory of Molecular Engineering of Polymers, Shanghai China
Herein, we develop a coordination-induced assembly approach to prepare smart polysaccharide-based anticancer phototherapeutic nanoparticles with hyaluronic acid (HA), a near-infrared dye (cypate) and ferric ions (Fe3+). Through forming coordinate bonds towards Fe3+, cypate inhibits the multivalent interactions between anionic HA and Fe3+. In this way, gelation is prevented and uniform spherical nanoparticles are generated. The obtained smart HA/cypate nanoparticles (HCNPs) combine many beneficial features in a single delivery platform, not only tumor targeting and magnetic resonance imaging capability, but also tumor microenvironment responsiveness, including enzyme-triggered off/on fluorescence and pH-triggered enhancement in the photothermal effect, which further improve the efficacy of the phototherapy. After administered in vivo, the HCNPs could effectively target to the tumor cells, and subsequently, under localized laser irradiation, hyperthermia and reactive oxygen species are generated simultaneously to ablate cancer, demonstrating their potential clinical applications in the oncotherapy. The coordination-induced assembly strategy can be extremely useful in the preparation of other biomacromolecule-based nanocarriers.
9:00 PM - NM10.3.03
Transient Micromotors that Disappear When No Longer Needed
Emil Karshalev 1 , Chuanrui Chen 1 2 , Jinxing Li 1 , Fernando Soto 1 , Isaac Campos 1 , Roxanne Castillo 1 , Fangzhi Mou 2 , Jianguo Guan 2 , Joseph Wang 1 Show Abstract
1 , University of California, San Diego, San Diego, California, United States, 2 , Wuhan University of Technology, Wuhan China
Proposed Symposium: Symposium NM10—Micro/Nano Assembling, Manufacturing and Manipulation for Biomolecular and Cellular Applications
Far from the simplistic micro/nano machines of the past, today’s small autonomous micro/nano machines have the ability to access low Reynolds number domains, utilize chemical and physical cues for self-propulsion and perform complex tasks in a variety of media.1 Despite this, micro/nano machines have been plagued by their unfavorable residues and toxic fuels. In order for micro/nanomachines to penetrate further into biomedical and environmental cleanup fields a virtually residue free micro machine has to be realized. We have combined multiple material systems to produce a set of truly transient micromachines which are capable of performing a task and then disappearing without a trace.2 Additionally, we have studied the degradation profiles of such micromachines to assess the mechanisms of breakdown helping us design systems with lifetimes across several orders of magnitude in several different media such as biofluid simulants. The development of such transient micromotors is a major step towards the successful integration of micro/nano sized machines into the human body and in environmental settings.
1.Wang. J, Nanomachines: Fundamentals and Applications, Wiley-VCH: Weinheim, Germany, 2013.
2.Chen et al. Transient Micromotors That Disappear When no Longer Needed. ACS Nano, 2016. In Press.
9:00 PM - NM10.3.04
Measuring the Viscoelastic and Adhesion Properties of Neurite by Forced Peeling
Ze Gong 1 2 , Haipei Liu 1 , Ran You 3 , Chuen-Chung Chang 3 , Yuan Lin 1 Show Abstract
1 Mechanical Engineering, University of Hong Kong, Hong Kong Hong Kong, 2 Material Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 3 Department of Anatomy, University of Hong Kong, Hong Kong Hong Kong
Mounting evidence has shown that neuron-extracellular matrix (ECM) and neuron-neuron adhesion are essential for processes like neurite outgrowth and the formation of synapses where information is exchanged among neural cells. However, measuring the interactions between neurons and their micro-environment has always been challenging.
In this study, we probed the viscoelastic and adhesion properties of neural cells through forced peeling of well-developed neurite branches on a substrate with an AFM cantilever. To interpret the experimental data as well as extract information of key interest, a computational model was also developed where the neurite is treated as a standard linear viscoelastic solid while a cohesive law between the cell and the substrate is introduced to represent their attractive interactions. These descriptions were then implemented in the quasi-static implicit finite element method from which the peeling response of neurite can be simulated and compared to the measurement data. Our simulations suggested that the instantaneous and long-time moduli of neurite should be around 7.5 kpa and 2.8 kpa, respectively, with a characteristic time ~2s. In addition, the adhesion energy of the neurite-ECM interface is estimated to be of the order of 0.07 mJ/m^2. The validity of these results were further tested and verified by a series of relaxation tests conducted after peeling the neurite with different rates.
9:00 PM - NM10.3.05
Magnetically Actuated Microswimmer for pH Sensing and Cargo Delivery
Ming You 1 , Fangzhi Mou 1 , Jiajia Zhang 1 , Chong Ma 1 , Jianguo Guan 1 Show Abstract
1 , Wuhan University of Technology, Wuhan China
Natural biomotors are capable of moving autonomously and performing complex tasks at the same time. Enlightened by motile micro-organisms, growing efforts have been devoted into developing artificial micro/nanomotors (MNMs) which mimic the motion strategy and function of natural biomotors. Among the reported MNMs, magnetically driven motors are the most promising for in vivo application since they can be propelled by biocompatible magnetic fields far away, avoiding toxic fuels or by-products, and their motion direction and speed can be precisely controlled by adjusting external fields. There are two major types of magnetically actuated MNMs, helical microswimmer and sperm-like swimmer. In this work, a sperm-like microswimmer is fabricated by attaching a magnetic bead to one end of polymer-coated photonic crystal (PC) microchain. An uniform magnetic field is applied to maintain direction, and a perpendicular oscillating field enables the microchain swimmer to propel in the form of a sperm. The “tail” composed of pH-sensitive polymer-coated PC chain can respond to pH change in surrounding area and change its structural color accordingly, which endows the swimmers with pH sensing property, and the “head” of the swimmer is modified with carboxyl, allowing them to pick up and unload micro cargoes by forming and breaking hydrogen bonds. Considering that the motion speed and direction of the microswimmer can be accurately controlled, this swimmer is expected to complete in vivo tasks such as micro area sensing and targeted cargo delivery.
This work was financially supported by the National Natural Science Foundation of China (21474078, 51573144 and 51521001), the Natural Science Foundation of Hubei Province (2014CFB163 and 2015CFA003), the Top Talents Lead Cultivation Project of Hubei Province.
 C. Zhang, J. Wang, W. Wang, N. Xi, Y. Wang and L. Liu, Bioinspir Biomim 2016, 11, 056006.
 M. Liu, L. Pan, H. Piao, H. Sun, X. Huang, C. Peng and Y. Liu, ACS Appl Mater Interfaces 2015, 7, 26017-26021.
 W. Gao, X. Feng, A. Pei, C. R. Kane, R. Tam, C. Hennessy and J. Wang, Nano Lett 2014, 14, 305-310.
 A. M. Maier, C. Weig, P. Oswald, E. Frey, P. Fischer and T. Liedl, Nano Lett 2016, 16, 906-910.
 W. Luo, H. Ma, F. Mou, M. Zhu, J. Yan and J. Guan, Adv Mater 2014, 26, 1058-1064.
9:00 PM - NM10.3.06
Self-Propelled Floating Foam Minimotor for Oil Removal
Xiaofeng Li 1 , Jingjing Guo 1 , Fangzhi Mou 1 , Zhen Huang 1 , Leilei Xu 1 , Jianguo Guan 1 Show Abstract
1 , Wuhan University of Technology, Wuhan, Hubei, China
Oil spill has been considered as one of the most harmful contaminants in water for human life and ecosystem. Traditional materials for oil removal, including clay, activated carbon, natural fibrous sorbent and magnetic nanoparticles etc., are passive materials and usually suffer from low absorption efficiency and long separation time. The self-propelled motors, which could autonomously move and capture various cargoes in liquid medium, may provide an alternative strategy to efficiently treat oil contamination in water. In this presentation, we will demonstrate a hydrophobic foam minimotor and their capabilities for efficiently oil adsorption on the water surface. The foam minimotor are self-propelled in fresh water and sea water under Marangoni effect, and has a maximum speed of 25 mm/s and a long life time of 240 min due to the slow and continuous release of camphor asymmetrically from the stearic acid-modified motor. The excellent motion properties and surface hydrophobicity of the minimotors make them as “swimming” adsorbents for oil capturing and loading via hydrophobic and capillary effects. After oil adsorption, multiple hydrophobic foam minimotors can spontaneously assemble into moving organized structure on water, which further facilitates the recovery of the motors and the collected oil. Compared to traditional passive materials for oil removal, the as-developed hydrophobic foam minimotor could actively approach, capture, load and transport oil spills, holding a great promise for oil removal and environment remediation.
This work was financially supported by the National Natural Science Foundation of China (21474078, 51573144 and 51521001), the Natural Science Foundation of Hubei Province (2014CFB163 and 2015CFA003), the Top Talents Lead Cultivation Project of Hubei Province.
Wang, B.; Liang, W.; Guo, Z.; Liu, W., Chem. Soc. Rev. 2015, 44 (1), 336-361.
Pan, D.; Mou, F.; Li, X.; Deng, Z.; Sun, J.; Xu, L.; Guan, J., J. Mater. Chem. A 2016, 4 (30), 11768-11774.
Mou, F.; Pan, D.; Chen, C.; Gao, Y.; Xu, L.; Guan, J., Adv. Funct. Mater. 2015, 25 (39), 6173-6181.
9:00 PM - NM10.3.07
Micromanipulation and Selective Release of Inorganic Crystals via Actuation of Elastomeric Supports—Organization, Separation, and Assembly of Nano/Microparticles
Mark Rose 1 , Jay Taylor 1 , Stephen Morin 1 Show Abstract
1 , University of Nebraska Lincoln, Lincoln, Nebraska, United States
Challenges associated with the stability of the hard/soft interface stem from mechanical, thermal, and/or chemical mismatch which can lead to failure (e.g., through delamination or fracture of the hard material) when the system is stressed. Strategies aimed at mitigating these failure mechanisms include chemical bonding, mechanically-graded films, etc.; however, in some applications (e.g., particle sorting/delivery), the ability to tune the hard/soft interface such that inorganic particles can be manipulated and released, on demand, would be advantageous. We report an approach that enables control over the adhesion of morphologically distinct crystals to soft, elastomeric polymers. This approach relied on rational modification of the polymer surface chemistry and that of the surrounding environment as well as mechanical stress on the system. The understandings we gleaned from this ensemble study enabled us to synthesize hard/soft interfaces with predictable adhesion properties. We applied these understandings to the design of materials with mechanically-activated, selective delamination characteristics useful to the 2D manipulation, assembly, separation, and (selective) delivery of specific inorganic crystals from mixtures of different morphologies (e.g., 1D and 2D morphologies of metal oxides, such as ZnO). We believe our strategies are applicable to fundamental investigations in biominerialization and the rational design of surfaces for technologies that rely on hard/soft interfaces (e.g., soft biomedical devices). We emphasize the applicability of the reported strategies to the design of robotically actuated systems that enable, through mechanical deformations of elastic support substrates, the automated manipulation, separation, and assembly of mixtures of inorganic/organic crystals/particles and, by extension, cells and other biological structures of relevance to biomolecular/cellular investigations.
9:00 PM - NM10.3.08
Chuanrui Chen 1 2 , Fangzhi Mou 1 , Leilei Xu 1 , Joseph Wang 2 , Jianguo Guan 1 Show Abstract
1 , Wuhan University of Technology, Wuhan China, 2 , University of California, San Diego, San Diego, California, United States
Self-propelled artificial micro/nanomotors have attracted increasing attention during the past decade because of their potentiation applications in biomedical and environmental fields. However, all the so far reported chemically propelled micro/nanomotors require asymmetric complex structures, making the driving force change constantly due to the severe interference of Brownian motions and local liquid flow. Thus, they can only perform curved or random motions. Here we introduce isotropic semiconductor micromotors with controlled phototactic motion. They move with a controllable motion direction and speed by sensing the incident light and subsequently generating chemical substances, regardless of the Brownian rotation of themselves. These bio-inspired micromotors can precisely manipulate particles by taking advantages of the light controlled phoretic attraction to the passive particle cargoes, which is quite intrigued for the future micro/nano-engineering. Furthermore, the isotropic structure of the micro/nanomotors has greatly simplified the fabrication process, remarkably beneficial for the large-scale production and application of micro/nanomotors. Our findings have provided a new way to design micro/nanomotors and may stimulate the exploitation of the microfabrication, microfluids and micro/nano-engineering.
9:00 PM - NM10.3.10
Ultrahigh Performance Electrically Driven Nanomotors—For Controllable Biomolecule Release, Purification and Microfluidic Manipulation
Jianhe Guo 1 , Kwanoh Kim 1 2 , Xiaobin Xu 1 3 , Donglei (Emma) Fan 1 Show Abstract
1 , University of Texas at Austin, Austin, Texas, United States, 2 , Korea Institute of Machinery and Materials, Daejeon Korea (the Republic of), 3 , University of California, Los Angeles, Los Angeles, California, United States
Nanomotors, which can convert diverse input energy sources to mechanical motions, are a type of device critical for further advancing nanoelectromechanical system (NEMS) devices. The development and application of these nanomotors devices are among the most pressing challenges in current nanoscience and nanotechnology. In this study, we presented an innovative strategy of assembly and rotation of rotary nanomotors driven by electric tweezers, and the demonstration of their applications in controllable biomolecule release, purification, and microfluidic manipulation. The electric tweezers, a recently invention of nano-manipulation technique, utilized electrophoretic (EP) forces to transport the nanoentities in DC electric fields, and dielectrophoretic (DEP) torques to align the nanoentities in their long direction in AC electric fields. Based on the electric tweezers, the rotary nanomotors are bottom-up assembled precisely and efficiently from nanoscale building blocks, which can be mass fabricated and less than 1 μm in all dimensions. After assembling, the rotary nanomotors achieved an ultra-fast speed up to 18,000 rpm and an ultra-durable operation lifetime of 80 hours and over 1.1 million total rotation cycles. They are applied for controllable biomolecule release and purification, demonstrating that adsorption and release rate of biomolecules on nanoparticles can be precisely tuned by mechanical rotations. The surface-enhanced Raman scattering (SERS)-active nanomotor is able to effectively monitor the concentration of biomolecules in real time. By integrating in the microfluidic channels, these nanomotors further realize the function of pumping and mixing for biomedical microfluidic devices. The innovations demonstrated in this work open a new, facile, and rational route in realizing many promising applications of nanomotors in biomedical and NEMS/MEMS devices.
9:00 PM - NM10.3.11
Electric Field Guided Manipulation of Chemically Powered Nanomotors for Application in Cargo Delivery, Assembly and Power of Rotary NEMS
Jianhe Guo 1 , Jeremie Gallegos 1 , Ashley Tom 1 , Donglei (Emma) Fan 1 Show Abstract
1 , University of Texas at Austin, Austin, Texas, United States
In this study, for the first time, we demonstrate controlled manipulation of chemically powered nanomotors by electric tweezers for applications in cargo delivery to designated microdocks and assembling of nanomotors for powering rotary nanoelectromechanical system (NEMS) devices. With the electric tweezers, based on the combined AC and DC electric fields, the motions of the nanorod motors can be readily aligned along the direction of the AC electric fields and the speed can be readily tuned by the DC electric fields. A large array of nanomotors can be transported along arbitrary trajectories with tunable speeds by the applied DC E-field. Assisted with the electric fields applied in the vertical direction by a three orthogonal microelectrode setup, the transport of nanomotors can be instantly initiated and stopped in the 2-D X-Y plane or moved in the vertical direction at a suitable fuel concentration. With strategically designed microelectrodes, we further realize reversible collection behaviors of chemically powered nanomotors, where a large group of nanomotors can be simultaneously collected and released on demand. Finally, the powerfulness of the manipulation of chemically powered motors by the electric tweezers is demonstrated in two applications: firstly, without any additional magnetic assistance, we have deftly employed nanomotors to attach, transport, and release cargos to pre-patterned microdocks with induced electric fields. Secondly, we precisely assembled chemical nanomotors to power designed rotary NEMS and successfully drove the rotation. This work presents a new and facile approach in guiding the motions of chemical motors for many promising applications.
9:00 PM - NM10.3.12
Magnetically Reconfigurable Microbots Based on Assemblies of Anisotropic Colloidal Particles
Koohee Han 1 2 , C. Shields 1 2 3 , Bhuvnesh Bharti 1 4 , Gabriel Lopez 2 5 , Orlin Velev 1 2 Show Abstract
1 Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, United States, 2 , Research Triangle Materials Research Science and Engineering Center, Durham, North Carolina, United States, 3 Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States, 4 Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, Louisiana, United States, 5 Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico, United States
Advances in microbotics have shown promise for micromanipulation and biomedical applications such as targeted diagnosis and drug delivery, yet the function of current microbots is still limited due to their single rigid body. We present a bottom-up approach for assembling metallo-dielectric microcubes into programmably and dynamically reconfigurable microbots under external magnetic fields. The building block, polymeric cube-shaped microparticles with a cobalt (Co) patch along one face, has been manufactured using photolithography followed by metal evaporation. Application of external magnetic field may selectively magnetize the Co-coated facets and assemble the metallo-dielectric cubes into linear, multi-cube chains where the Co patches are oriented in series along the center of the assembled chains. More importantly, the polarization patterns of the Co patches can be modulated by tuning field parameters (e.g., field strength, frequency and direction), leading to dynamic reconfiguration of the assembled chains. On this basis we have demonstrated how such field-directed reconfigurable assemblies can play an unprecedented role for micromanipulation by making microbot prototypes. Firstly, their potential is illustrated by making a micro-grabber capable of grabbing and transporting microscale objects (e.g., biological cells). The micro-grabber can be remotely and precisely controlled by combining uniform magnetic field controlled folding actuation and field gradient driven spatial navigation. In addition to that, we have also shown that such field-driven microbot assemblies can serve as analytical tools for colloidal and biological systems. The dynamic reconfigurability of the assembled clusters at micron-scale can be used to locally probe a microenvironment such as investigating the local organization of liquid crystal molecules and measuring the rigidity of microscopic specimens (e.g., living cells, vesicles).
9:00 PM - NM10.3.13
Acoustically Propelled Nanoshells—New Advances in Acoustically Propelled Nanomotors
Joseph Wang 1 , Fernando Soto 1 Show Abstract
1 , University of California, San Diego, San Diego, California, United States
Recent advances in the field of acoustically-powered nanomachines, triggered by ultrasound waves, have opened the door for new breakthrough biomedical applications.1,2 These exerted sound waves used are relatively innocuous and easy to manipulate, offering unique advantages for enabling efficient and controllable motion in different biological media.
This presentation will address a new a design of acoustic nanoswimmers,3 based on a nanoshell geometry, fabricated by a sphere template process. Furthermore, a detailed study of the parameters that affect the nanoshell propulsion (material density, size, and shape), indicates that the nanoshell motors exhibit a different propulsion behavior than that those predicted by recent theoretical and experimental models for acoustically-propelled nanomotors.4,5 The practical application of the nanoshell was demonstrated by performing complex tasks, such as the capture and transport of multiple cargoes and the internalization and propulsion of the nanoshells inside live MCF-7 cancer cells. These new insights into acoustically propelled nanomotors could lead the way to design novel fuel-free nanoswimers capable of performing complex tasks for diverse biomedical applications.
1. V. Garcia-Gradilla, J. Orozco, S. Sattayasamitsathit, F. Soto, F, Kuralay, A. Pourazary, A. Katzenberg, W. Gao, Y. Shen and J. Wang, ACS Nano, 2013, 7, 9232−9240.
2. W. Wang, S. Li, L. Mair, S. Ahmed, T. J. Huang and T. E. Mallouk, Angew. Chem., Int. Ed., 2014, 53, 3201-3204.
3. F. Soto, Gregory L. Wagner, V. Garcia-Gradilla, K.T. Gillespie, D. R. Lakshmipathy, E. Karshalev, C. Angell, Y. Chen and J. Wang, Nanoscale, 2016, DOI: 10.1039/C6NR06603H,
4. S. Ahmed, W. Wang, L. Bai, D. T. Gentekos, M. Hoyos and T.E. Mallouk, ACS Nano, 2016, 10, 4763-4769.
5. F. Nadal and E. Lauga, Phys. Fluids, 2014, 26, 082001.
9:00 PM - NM10.3.14
Biocide Activity of Microporous Titanosilicate ETS-10 Containing Volatile Organic Compound Thymol
Melda Isler Binay 1 , Burcu Akata Kurc 1 2 Show Abstract
1 Micro and Nanotechnology Department, Middle East Technical University, Ankara Turkey, 2 Central Laboratory, Middle East Technical University, Ankara Turkey
Biocide volatile essential oils extracted from plants, such as thymol, have become known as promising alternative antimicrobial agents to synthetic pesticides [1, 2]. However, due to its volatile property, it can easily lose their biocide activity before contacting with microorganisms . Encapsulation in porous structure is a proper way to control of release and provides effective biocide activity. In this study, firstly, Engelhard titanosilicate ETS-10 was synthesized and post-synthesis treatment of ETS-10 was performed in order to absorb thymol molecules. Secondly, the antibacterial activity of ETS-10 crystals, absorbed thymol molecules, was performed against gram-negative bacterium E. Coli for the first time. Engelhard titanosilicate ETS-10 is a microporous crystalline material (pore dimensions: 4.9 Å and 7.6 Å) where its Ti substituted silica matrix is composed of Si in tetrahedral and Ti in octahedral coordination. The enlargement of micropores in ETS-10 crystals was performed by post-synthesis treatment with an aqueous H2O2 solution, resulting in leaching of titania chains . As-synthesized ETS-10 and treated ETS-10 crystals were analyzed by XRD, SEM, BET and ICP-OES techniques. Biocide activity assays were performed by disk diffusion assay. Greater zone of inhibition (20 mm) were obtained from the treated ETS-10 samples when compared to one of as-synthesized ETS-10 (12 mm), showing enlarged porosity in the structure of the zeolite matrix making it possible for the organic molecule to penetrate into the framework leading to enhanced biocide activity.
 R. J. W. Lambert, P.N. Skandamis, P.J. Coote and G.-J.E. Nychas, Journal of Applied Microbiology 91 (2001) 453-462.
 J. Xu, F. Zhou, B.-P. Ji, R.-S. Pei and N. Xu, Letters in Applied Microbiology 47 (2008) 174–179.
 A. Janatova, A. Bernardos, J. Smid, A. Frankova, M. Lhotka, L. Kourimska, J. Pulkrabea, P. Kloucek, Industrial Crops and Products 67 (2015) 216–220.
 C. C. Pavel, S. Park, A. Dreier, B. Tesche, and W. Schmidt, Chem. Mater. 18 (2006) 3813-3820.
Donglei (Emma) Fan, University of Texas at Austin
Xiaodong Chen, Nanyang Technological University
Peer Fischer, Max Planck Institute for Intelligent Systems
Tony Huang, Duke University
NM10.4/SM8.5: Joint Session: Functional Materials for Cellular and Biotechnological Applications
Wednesday AM, April 19, 2017
PCC West, 100 Level, Room 102 AB
9:30 AM - NM10.4.01/SM8.5.01
Regulation of Mesenchymal Stem Cell Behavior and Secretion via Microscale Surface Roughness
Nan Ma 1 , Xun Xu 1 , Weiwei Wang 1 , Zhengdong Li 1 , Jie Zou 1 , Karl Kratz 1 , Andreas Lendlein 1 Show Abstract
1 , Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow Germany
Mesenchymal stem cells (MSCs) are capable of differentiating into multiple lineages for cell-based regenerative therapies. Recent developments in biomaterials have indicated that the physicochemical natures of materials strongly influence self-renewal, differentiation and secretome profile of MSCs [1-2]. As a complement to traditional biochemical methods, there is a great promise to use physical approach such as roughness to instruct the behavior and paracrine capacity of MSCs to optimize their therapeutic potential. Here, as a model system, both polystyrene and poly (ether imide) surfaces with three roughness levels were fabricated: R0 (smooth), R1 (with roughness level comparable to cell size) and R2 (with roughness level greater than cell size). To ensure that the cells were only in contact to the material itself, MSCs were cultured in closed polymer cups with distinct roughness on bottom surfaces, which were processed via injection molding . In this study, despite a high cell viability was shown on all polymeric substrates, the apoptotic and senescent levels were highly modulated by roughness. The apoptotic level and the ratio of senescent MSCs on R1 were lower than those on smooth R0 surface. Moreover, the secretion of pro-angiogenic factors of MSCs on R1 was remarkably upregulated compared to R0 and R2 and the enhancement of those factors could be abolished via blockage of focal adhesion associated signaling pathway. In summary, the polymeric substrates with surface roughness R1 provide more superior surface environment for MSCs cultivation in respect to apoptosis, senescence and secretion. Therefore, roughness might be an important parameter to be considered for advanced biomaterial design.
 Phillips JE, Petrie TA, Creighton FP, García AJ. Acta Biomater. 2010, 6, 12-20.
 Lee J, Abdeen AA, Zhang D, Kilian KA. Biomaterials. 2013, 34, 8140-8148.
 B. Hiebl, K. Lutzow, M. Lange, F. Jung, B. Seifert, F. Klein, T. Weigel, K. Kratz and A. Lendlein. J Biotechnol. 2010, 148, 76-82.
9:45 AM - NM10.4.02/SM8.5.02
Fabrication of Crosslinked Sphere Structure of Biodegradable Polymer Nanoparticles for Efficient Controlled Drug Release
Ravichandran Honnavally Kollarigowda 1 , Anu Stella Mathews 1 , Sinoj Abraham 1 , Carlo Montemagno 1 Show Abstract
1 Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, Canada
Polymeric materials producing nanomaterials in the form of nanoparticles, nanorods, nanowires, nanotubes, thin films, etc. is the key element for the success of the nanotechnology, which gives extraordinary physical and chemical properties as a result of its nanosize.1-3 There have been proposals for numeral applications in the field of biomedicine, and some of them (such as sensors of DNA, the controlled release of drugs, tumor therapy, etc.) are close to achieving a successful development.4 Drug delivery systems developed through the combination of biocompatible materials and biodegradable constitute an important area of focus in the engineering of medical devices. In view of this, we Synthesized set of cross-linked sphere biodegradable polycaprolactone (PCL) nanoparticles with and without out cross linker via oil/water solvent evaporation method. PCL was synthesized by ring opening polymerization technique using metal oxide as a catalyst and alcohol as an initiator, furthermore, they are modified with a photocrosslinking agent as the end groups. The nanoparticles (Nps) were synthesized by crosslinking the hydrophobic tail by UV light irradiation and hydrophilic drug was encapsulated by sonication method with the presence of stabilizer (polyvinyl alcohol). The crosslinked nanoparticle size was monodisperse with narrow size (~100 nm) whereas solitary PCL nanoparticles were poly disperse with higher diameter (>500nm). Transmission electron microscopy (TEM) analysis revealed that these nanoparticles are assembled with hydrophobic tail structures cross-linked tail on outer sphere. The drug encapsulation efficiency controlled release is mainly influenced by the molecular weight and outer sphere content of the nanoparticles structure. The drug encapsulated crosslinked nanoparticles exhibit a pH-dependent release behavior in vitro, within 60 hours the complete drug was released in all the three pH condition pH 4, 5 and 7.4. Importantly, this novel nanoparticles system for cytotoxicity studies were carried out with cancer cell lines and it was found that these NPs system were biocompatible. Encapsulation of drug with cross-linked NPs shows comprehensive results, justifying the potential use of drugs with greater absorption cellular, sustained release, and retard the cancer cells.
Overall, these results suggest that cross-linked outer sphere biodegradable nanoparticle system are likely to have a great potential as therapeutic agents.
1. K. Avgoustakis, A. Beletsi, Z. Panagi, P. Klepetsanis, A. G. Karydas and D. S. Ithakissios, J. Control. Release, 202, 79, 123–135.
2. L. Brannon-Peppas, int. J. Pharm, 1995, 116, 1-9.
3. R. H. Kollarigowda, RSC Advances, 2015, 5, 102143-102146.
4. R. CP, N. RJ, R. AJ and V. F, Nanomedicine, 2006, 2, 8-21.
10:00 AM - NM10.4.03/SM8.5.03
Maintenance of Neural Progenitor Cell Stemness in 3D Hydrogels Requires Matrix Remodeling
Christopher Madl 1 , Ruby Dewi 1 , Cong Dinh 1 , Kyle Lampe 1 2 , Duong Nguyen 3 , Annika Enejder 3 , Sarah Heilshorn 1 Show Abstract
1 , Stanford University, Stanford, California, United States, 2 , University of Virginia, Charlottesville, Virginia, United States, 3 , Chalmers University of Technology, Gothenburg Sweden
While neural progenitor cells (NPCs) hold significant therapeutic promise, the difficulty and cost of expanding a large number of stem cells remains a significant barrier to widespread clinical use. Recently, 3D hydrogels have been proposed as in vitro culture platforms for the expansion of stem cell populations to overcome the space limitations of 2D culture. However, very little is known about what 3D material properties are required to maintain NPCs in an undifferentiated state for expansion. It is well-established that matrix stiffness modulates stemness in strongly adherent stem cells, including mesenchymal stem cells and muscle satellite cells, but the impact of stiffness on stemness maintenance in non-adhesion-dependent stem cells such as NPCs is not well known. Furthermore, within 3D materials, matrix degradability is another crucial design parameter that can modulate stem cell behavior, as previous studies have shown that cells cannot spread, migrate, or proliferate without first degrading their surrounding matrix. To investigate the impact of matrix stiffness and degradability on NPC stemness, we designed a family of modular, engineered elastin-like protein (ELP) hydrogels with varying stiffness (E~0.5-50 kPa) and degradability. These ELP gels consisted of structural domains derived from elastin to provide tunable stiffness and bioactive domains to permit cell adhesion and matrix degradation. Strikingly, expression of the stem markers Nestin and Sox2 by embedded NPCs was not correlated with hydrogel stiffness over the range tested. However, expression of stem markers was strongly correlated with hydrogel degradability, with increased stem maintenance in more degradable hydrogels. NPCs cultured in high degradability hydrogels exhibited increased proliferation and enhanced differentiation potential, confirming that increased degradability was associated with maintenance of a functional stem phenotype. We identified that NPCs utilize the protease ADAM9 to regulate matrix remodeling in the ELP gels. Accordingly, knockdown of ADAM9 inhibited NPC-mediated hydrogel degradation and resulted in a loss of stemness. To confirm that ADAM9-mediated remodeling is a generalizable mechanism for maintaining NPC stemness in 3D, we designed a second hydrogel system based on peptide-crosslinked poly(ethylene glycol) with independent tuning of stiffness (E~0.5-2 kPa) and ADAM9 degradability. Consistent with our findings using the ELP gels, stemness was maintained in hydrogels susceptible to degradation by ADAM9 independent of stiffness, while non-ADAM9 degradable gels resulted in a loss of NPC stemness. Our results have identified matrix remodeling as a previously unknown requirement for maintenance of NPC stemness in 3D hydrogels and suggest that ADAM9-degradable materials may be useful for expansion of therapeutically relevant numbers of undifferentiated NPCs.
10:15 AM - NM10.4.04/SM8.5.04
Selective Packaging of pDNA into Rod- or Toroid-Shape within Polyplex Micelles
Kensuke Osada 1 , Yanmin Li 1 , Kazunori Kataoka 2 1 Show Abstract
1 , University of Tokyo, Tokyo Japan, 2 , Innovation Center of NanoMedicine (iCONM) , Kawasaki Japan
DNA undergoes large conformational transition from hydrated coil to dehydrated compact form upon polyion complexation (PIC) with polycations. The volume transition, called DNA condensation, receives remarkable attention because this is essential of the nucleosome formation and is an important part in preparation of gene delivery system. In this study, using block catiomers composed of poly(ethylene glycol) (PEG) and polycations, condensation behavior of plasmid DNA (pDNA) was investigated to accommodate a fundamental interest; how the micrometer-length pDNA changes its conformation and packaged into 100 nm-sized PIC assembly, namely polyplex micelles (PMs), within the constraint of inherent rigidity of the double-stranded DNA. Moreover, the packaged pDNA structure was attempted for control into particular ordered structures, as they are acknowledged to be relevant for eliciting biofunction of pDNA. Here, we show a success of selective packaging of pDNA into either rod-like structure or toroidal structure by modulating interactive potency between pDNA and block catiomers to form PMs, and explored potential biological activities of each structure as a gene delivery system. Interestingly, the toroid-shaped structure held intriguing biological functions; not only capable of elevating in vitro transcription efficiency but also of elevating in vivo gene transduction efficiency compared to the rod-shaped structure, which have been addressed as potent delivery system. This result demonstrated a tempting utility of the toroid structure as a novel-structured gene delivery system.
10:30 AM - *NM10.4.05/SM8.5.05
Metal-Organic Frameworks for Biotechnology
Paolo Falcaro 1 , Raffaele Ricco 1 Show Abstract
1 , TuGraz, Graz Austria
Among the different classes of Metal-Organic Framework (MOF) composites prepared during recent years using ceramic, metallic and polymeric nanoparticles,1,2,3,4 a new emerging type of MOF composite has been recently obtained encapsulating bio-macromolecules within MOFs.5,6,7 Thanks to different water-based synthetic approaches such as co-precipitation and biomimetic mineralization methods, different types of MOFs have been self-assembled around bio-active compounds (e.g. enzymes). These new bio-composites have shown unprecedented properties for the protection and release of proteins. This strategy enables the fast encapsulation of guests larger than micropores of MOFs. Remarkably, this novel approach overcomes the need for MOFs with pores larger than the hosted biomolecules, and enable one-pot syntheses as an alternative preparation route to post infiltration methods.8 Thus, MOFs are now considered promising materials for biotechnological applications as the encapsulation technique is inexpensive, effective and fast.6
In this presentation, an overview ranging from the exploitation of simple proteins and their constituents (amino acids)9 to complex biological systems for the formation of MOFs will be provided. The functional properties of these composites will be disclosed providing examples of other methods used for the encapsulation of proteins within MOFs, including the preparation of hollow MOF capsules.11,12 Comparison of the protective properties will be illustrated10 and the applications of proteins for the controlled localization of MOFs discussed.13 The exciting challenges and promising applications of these new MOF composites in biotechnology will be presented.
(1) Falcaro, Ricco, Yazdi, Imaz, Furukawa, Maspoch, Ameloot, Evans, Doonan Coord. Chem. Rev. 2016.
(2) Zhu, Xu Chem Soc Rev 2014.
(3) Doherty, Buso, Hill, Furukawa, Kitagawa, Falcaro, Acc. Chem. Res. 2014.
(4) Li, Kobayashi, Taylor, Ikeda, Kubota, Kato, Takata, Yamamoto, Toh, Matsumura, Kitagawa Nat. Mater. 2014.
(5) Lyu, Zhang, Zare, Ge, Liu, Nano Lett. 2014.
(6) Liang, Ricco, Doherty, Styles, Bell, Kirby, Mudie, Haylock, Hill, Doonan, Falcaro Nat. Commun. 2015.
(7) Shieh, Wang, Yen, Wu, Dutta, Chou, Morabito, Hu, Hsu, Wu, Tsung J. Am. Chem. Soc. 2015.
(8) Lykourinou, Chen, Wang, Meng, Hoang, Ming, Musselman, Ma J. Am. Chem. Soc. 2011.
(9) Liang, Riccò, Doherty, Styles, Falcaro CrystEngComm 2016.
(10) Liang, Coghlan, Bell, Doonan, Falcaro Chem Commun 2016.
(11) Huo, Aguilera-Sigalat, El-Hankari, Bradshaw Chem. Sci. 2014.
(12) Jeong, Ricco, Liang, Ludwig, Kim, Falcaro, Kim Chem. Mater. 2015.
(13) Liang, Carbonell, Styles, Ricco, Cui, Richardson, Maspoch, Caruso, Falcaro Adv. Mater. 2015.
11:00 AM - NM10.4/SM8.5
11:30 AM - NM10.4.06/SM8.5.06
Mimicking Matrix Vesicles to Enhance Biomineralization of Osteoblast Cells
Fabian Itel 1 , Brigitte Stadler 1 Show Abstract
1 , Aarhus University, Aarhus Denmark
Load-bearing implants such as artificial hip or knee joints require a stable interface with bone tissue. Bioactive glass or bioactive ceramics as bulk implants or as surface coatings have so far proven to be the most successful concepts used in clinics due to their ability to induce osteoconduction or even osteostimulation. However, these ceramic and glass implants are difficult to fabricate and suffer from selective mechanical properties. Here, we aim to improve the osteoconduction of bone-forming osteoblast cells by providing a triggered mineralization at the bone tissue-implant interface. Specifically, we develop a kick-start for osteoblasts to produce extracellular matrix (ECM) and mineralization and, thus, provide a faster integration of implants within bone tissue. Our approach involves the assembly of artificial bone cells, which are composed of ECM components and matrix vesicles (MVs). Both components are important for the initial mechanism of bone mineralization. MVs are 100 nm-sized phosphatidylserine- (PS) and alkaline phosphatase (AP)-containing liposomes secreted by osteoblasts. Calcium phosphate (CaP) crystals are formed within MVs and adhere to the ECM of bone tissue, where further mineralization takes place on collagen fibrils. Our artificial bone cells are assembled in two different ways to form “soft” and “hard” microparticles using droplet-microfluidics to form agarose (hydrogel) microbeads and the layer-by-layer technique to assemble core-shell particles, respectively. Our key requirements are that the artificial bone cells i) have similar sizes to biological osteoblasts, ii) are composed of collagen fibers and iii) contain artificial MVs composed of PS-containing liposomes with encapsulated AP enzymes. AP cleaves phosphate ions from phosphomonoester substrates, which can be added to the cell media and induces CaP crystallization. Furthermore, the particle surface is crucial for cell adherence and cell interaction. Therefore, different surface coatings are employed including polydopamine, poly-L-lysine, collagen, and growth factors. The “soft” and the “hard” artificial bone cells are then compared by coculturing them with bone-forming Saos-2 cells (sarcoma osteogenic cells). The rate of mineralization is assessed by quantifying the produced mineral content and the number of cells in presence or absence of the artificial bone cells. We anticipate that our approach has the potential to enhance osteoblast-mediated bone formation.
11:45 AM - NM10.4.07/SM8.5.07
Micro-Fabricated Thermoresponsive Polymer-Grafted Surface for Producing Contractile Muscle Tissue Construct
Hironobu Takahashi 1 , Tatsuya Shimizu 1 , Masayuki Yamato 1 , Teruo Okano 1 Show Abstract
1 , Tokyo Women's Medical University, Tokyo Japan
Complex structural organization in the body is a key factor to produce the appropriate tissue functionality. In mature skeletal muscle, for example, the muscle fibers are highly oriented to produce its mechanical functions. To engineer biomimetic tissues, therefore, a technique for mimicking microstructures in native tissues is required. Thermoresponsive poly(N-isopropylacrylamide) (PIPAAm)-grafted surface allows harvesting a cell monolayer as a single continuous cell sheet from the culture surface. Since cell sheets can be layered to produce 3D tissue construct, this cell sheet-based technology have been used effectively in the field of tissue engineering. In this study, a micro-fabricated thermoresponsive cell culture substrate was prepared to produce cell sheets composed of aligned cells. To control cell orientation in a cell sheet, stripe-shaped micro-patterns was fabricated on the thermoresponsive surface. Using this surface, we have engineered 3D muscle tissue having aligned orientation.
First, hydrophilic polyacrylamide (PAAm) was grafted spatio-selectively on a thermoresponsive surface through a photo-induced polymerization process. As a result, stripe patterns of PAAm-co-PIPAAm and PIPAAm regions (50 μm / 50 μm) was fabricated. Muscle progenitor cells, myoblasts, were aligned on the surface and reached to confluence by seeding onto the surface at 37 °C. Next, to produce a 3D tissue construct, multiple cell sheets were harvested from the surface and then layered using a gelatin gel-coated manipulator. Using this technique, multiple cell sheets were successfully layered while maintaining the cell orientation as designed. Interestingly, in the tissue construct, it was observed that aligned myoblasts changed their orientation by themselves. For example, when two cell sheets composed of aligned myoblasts were layered perpendicularly, all myoblasts of the bottom sheet re-oriented in the same direction of the top cell sheet. Using this unique behavior of myoblast, an aligned myotube construct was able to be produce by layering one aligned cell sheet and two random cell sheets. The randomly-oriented myoblasts were finally well aligned within the multilayer cell sheet construct through the self-organization process. Furthermore, the tissue construct was transferred onto a collagen gel and incubated in differentiation medium for 3 weeks. The resultant myotubes contracted by electrical pulse stimulation. Importantly, the muscle contraction was regulated directionally because of the aligned orientation of the construct.
In conclusion, we have developed a novel technique to create a muscle tissue construct through a cell sheet layering process. Uniquely, myoblasts self-organized their orientation within the tissue construct and showed regulated contraction by electrical stimulation. This structural design and functionalization could lead to truly biomimetic tissue generation, and development of in-vitro physiological tissue models.
12:00 PM - *NM10.4.08/SM8.5.08
Mechanobiology, Pluripotent Stem Cells, and Early Embryonic Development
Jianping Fu 1 Show Abstract
1 , University of Michigan, Ann Arbor, Ann Arbor, Michigan, United States
Research on human pluripotent stem cells (hPSCs) has significant promise for regenerative medicine, disease modeling, and developmental biology studies. In this talk, I will discuss our effort in leveraging the mechanobiology of hPSCs in conjunction with some synthetic biomimetic systems to recapitulate and model human early embryonic development. I will first discuss our effort in constructing microengineered stem cell models of early human neurological developmental processes. Specifically, we have utilized microengineered hPSC cultures to develop autonomously regionalized neuroectoderm tissues in vitro. Importantly, our findings have suggested that induction and regionalization of neuroectoderm tissues involve mechanically gated molecular signaling (including Wnt, Hippo, and BMP) through regulations of cell shape and cytoskeleton contractility to reinforce spatial patterning of cell fates in neuroectoderm tissues. Together, our data provide strong evidence supporting critical involvements of cellular mechanics and mechanobiology as control mechanisms in ensuing robust formation of regionalized neuroectoderm tissues. In the last part of my talk, I will describe an efficient method to generate early human amniotic tissue in vitro through self-organized development of hPSCs in a bioengineered niche that mimics the in vivo implantation environment. Biophysical signals from the implantation-like niche act as a switch to toggle hPSC self-renewal versus amniogenesis. Our study unveils a self-organizing nature of human amniogenesis and establishes the first hPSC-based model system for investigating peri-implantation human amnion development.
12:30 PM - NM10.4.09/SM8.5.09
Stabilization of Enzymes Using a Protein Matrix Identified from Squid Sucker Ring Teeth
Chelsea Riegel 1 2 , Patrick Dennis 1 , Marquise Crosby 1 , Matthew Dickerson 1 , Rajesh Naik 3 Show Abstract
1 Materials and Manufacturing Directorate, Air Force Research Laboratory, Wright-Patterson Air Force Base, Ohio, United States, 2 , UES Inc, Dayton, Ohio, United States, 3 711 Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Ohio, United States
Protein entrapment has demonstrated great promise in the area of enzyme and biomolecule stabilization. Silk fibroin derived from the Bombyx mori silkworm, has been shown to stabilize a number of biomolecules including enzymes, vaccines and antibiotics. This is due to the highly repetitive amino acid structure of silk fibroin which lends the ability to self-assemble into ordered microcrystalline domains. The ordered structure of silk fibroin is hypothesized to create a “molecular crowding” regime where biomolecules and enzymes are stabilized through the prevention of unfolding. Based on the success of silk fibroin as a stabilizing excipient, we have looked at other potential protein matrices for their ability to stabilize labile biomolecules. The protein, suckerin-12 (S12), derived from the sucker ring teeth of the Humboldt squid, offers unique properties and potential advantages over silk fibroin, including a greatly reduced monomeric molecular weight, a more defined repeat structure and the ability to express large amounts of the protein recombinantly. Recently, S12 based hydrogels have been investigated for their shape changing properties, where under certain buffer conditions, they are induced to condense into a dehydrated state, reversibly. The potential for tunable molecular crowding led us to investigate whether S12 based hydrogels have the ability to protect labile enzymes from environmental insults. Here we present the effects of enzyme adsorption into S12 hydrogels in terms of heat stability and the ability to withstand a number of chemical insults. In this study, the ability of S12 hydrogels to protect enzymes from damage is compared to that of silk fibroin.
12:45 PM - NM10.4.10/SM8.5.10
Systemic Administration of Enzyme-Responsive Nanocapsules for Promoting Bone Repair
Hongzhao Qi 1 , Xiaolei Sun 2 , Xue Li 3 , Zhaoyang Li 1 , Jin Zhao 1 , Xin Hou 1 , Xubo Yuan 1 , Yunde Liu 3 , Zhenduo Cui 1 , Yunfeng Lu 4 , Xianjin Yang 1 Show Abstract
1 Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin China, 2 , Department of Orthopedics, Tianjin Hospital, Tianjin China, 3 Department of Clinical Microbiology, School of Laboratory Medicine, Tianjin Medical University, Tianjin China, 4 Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California, United States
Accelerating the healing of fractures and bone defects by local delivery of growth factors possessing osteoinductive activity has been extensively demonstrated. Unfortunately, fractures, such as osteoporotic vertebral compression fracture, are incapable of adopting such strategy because of the difficulty of surgery or in situ injection. Systemic administration of growth factors is considered to be the appropriate solution for these diseases. But the therapy was hampered by the poor in vivo stability of growth factors, inefficient distribution in fracture site and the potential side effects such as ectopic osteogenesis. To address this challenge, we here conceived a growth factor systemic delivery platform based on nanocapsules possessing bone fracture-targeting ability and enzyme-responsive releasing ability, taking the advantages of the unique physiological character of bone fracture, i.e., the rupture and leakage of blood vessels and the over-expression of matrix metalloproteinases (MMP). Bone morphogenetic protein-2 (BMP-2), 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and MMP-degradable peptide were chosen as the model growth factor, monomer and crosslinker, respectively. Electrostatic and hydrogen bonding interactions enriched the monomers and crosslinkers around BMP-2 molecules and in situ free radical polymerization formed a thin polymer layer around BMP-2s, forming the nanocapsules with controlled composition. These nanocapsules are of uniform small size (~30 nm) possessing long circulation time (half-life is ~40 h) and can be passively targeted to fracture site through the ruptured and leaked blood vessels after systemic administration. Once accumulated in fracture site, the shells of nanocapsules could be degraded by MMP and thus BMP-2s were released. Animal experiments prove BMP-2 nanocapsules show better bone repair ability than native BMP-2. Furthermore, owe to the improvement of biodistribution of BMP-2 and the enzyme-responsive releasing characteristic, systemic administration of BMP-2 nanocapsules didn’t cause obvious ectopic osteogenesis. The results of this study demonstrate nanocapsules can enhance the in vivo stability and fracture sites delivery efficiency of growth factors and avoid their ectopic osteogenesis potential, realizing the repair of bone fracture by systemic administration of growth factors.
NM10.5: Nanomanipulation and Nanomotors III
Wednesday PM, April 19, 2017
PCC West, 100 Level, Room 102 AB
2:30 PM - *NM10.5.01
Dynamics of Self-Assembled Active Colloids
John Gibbs 1 , Amir Nourhani 2 , Joel Johnson 1 , Paul Lammert 2 Show Abstract
1 , Northern Arizona University, Flagstaff, Arizona, United States, 2 Physics, Pennsylvania State University, University Park, Pennsylvania, United States
Active colloidal Janus particles show intriguing behavior once self-assembled into active clusters. We find that certain configurations become dominant as the concentration of fuel increases, suggesting these clusters are more stable when higher propulsive speeds are involved. We also explore the interaction and dynamics of active Janus particles in the presence of external fields.
3:00 PM - *NM10.5.02
Nanomachines that Write, Image, Repair, Sense, Isolate and Destroy
Joseph Wang 1 Show Abstract
1 , University of California, San Diego, San Diego, California, United States
The remarkable performance of biomotors has inspired scientists to create synthetic nanoscale machines that mimic the function of these amazing natural systems . Creative research efforts across the globe have led to powerful and versatile man-made nanomachines. Significant improvements in the capabilities of these nanoscale machines have led to greatly enhanced speed and power, motion control, cargo-towing force, versatility, functionality and scope of synthetic nanomotors. The greatly improved capabilities of artificial nanomotors have paved the way to exciting and important new applications. Our team has recently described nanoscale machines capable of ‘writing’ (patterning) nanoscale features, repairing electrical circuits, perform high resolution imaging, generating energy, isolating cancer cells, detecting intracellular targets, or sensing and neutralizing threats. These recent advances and capabilities will be described, along with future prospects and challenges.
1. J. Wang, “Nanomachines: Fundamentals and Applications”, Wiley, 2013.
4:30 PM - NM10.5.03
Collective Dynamics of Magnetic Colloidal Rollers
Alexey Snezhko 1 Show Abstract
1 , Argonne National Laboratory, Lemont, Illinois, United States
Strongly interacting colloids driven out-of-equilibrium by an external periodic forcing often develop nontrivial collective dynamics. The behaviors range from coherent vortical motion to phase separation and dynamic self-assembly. While colloidal systems are relatively simple, understanding their collective response, especially in out of equilibrium conditions, remains elusive. Ferromagnetic micro-particles immersed in water and sediment on the bottom surface of the flat cell are energized by a single-axis homogeneous alternating magnetic field applied perpendicular to the surface supporting the particles. Upon application of the alternating magnetic field the magnetic torque on each particle is transferred to the mechanical torque giving rise to a rolling motion of the particle. Experiments reveal a rich collective dynamics of magnetic rollers in a certain range of excitation parameters. Flocking and spontaneous formation of steady vortex motion have been observed. The effects are fine-tuned and controlled by the parameters of the driving magnetic field.
The research was supported by the U.S. DOE, Office of Basic Energy Sciences, Division of Materials Science and Engineering.
4:45 PM - NM10.5.04
Microrobotic Lithography and Nanoscopy
Jinxing Li 1 , Wenjuan Liu 1 , Tianlong Li 1 , Babak Bahari 1 , Wei Gao 1 , Boubacar Kante 1 , Joseph Wang 1 Show Abstract
1 , University of California, San Diego, San Diego, California, United States
Inspired by natural nanomachines, synthetic micro/nanoscale machines and robots have recently demonstrated remarkable performance and functionality. Here we show microrobot—could be integrated with optical functions to “write” and “read”—as new autonomous tools for nanolithography and nanoscopy.
Firstly, we introduce a new nano-patterning approach, named ‘nanomotor lithography’, which translates the autonomous movement trajectories of nanomotors into controlled surface features. As a proof of principle, we use metallic nanowire motors as mobile nanomasks and Janus sphere motors as near-field nanolenses to manipulate light beams for generating a myriad of nanoscale features through modular nanomotor design. The complex spatially defined nanofeatures using these dynamic nanoscale optical elements can be achieved through organized assembly and remote guidance of multiple nanomotors. Such ability to transform predetermined paths of moving nanomachines to defined surface patterns provides a unique nanofabrication platform for creating diverse nanodevices.
Secondly, we introduce a new imaging method, named swimming microrobot optical nanoscopy, based on untethered chemically powered microrobots as autonomous probes for subdiffraction optical scanning and imaging. The microrobots are made of high-refractive-index microsphere lenses and powered by local catalytic reactions to swim and scan over the sample surface. Autonomous motion and magnetic guidance of microrobots enable large-area, parallel and nondestructive scanning with subdiffraction resolution, as illustrated using soft biological samples such as neuron axons, protein microtubulin, and DNA nanotubes. Incorporating such imaging capacities in emerging nanorobotics technology represents a major step toward ubiquitous nanoscopy and smart nanorobots for spectroscopy and imaging.
1. J. Li et al Nature Communications, 2014, 5, 5026.
2. J. Li et al Nano Letters, 2016, DOI: 10.1021/acs.nanolett.6b03303.
5:00 PM - *NM10.5.05
Cellular Applications of Single Beam Acoustic Tweezer
K. K. Shung 1 , Hae Lim 1 Show Abstract
1 Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States
Single beam acoustic tweezer (SBAT), a counter part of optical tweezer but capable of generating larger forces, has been used to manipulate cells and microparticles as small as a few hundred nanometers in diameter. In addition to an application to estimating cellular deformability, more recently SBAT has been shown to be capable of measuring interactive forces between red blood cells which can be quantitated with a micropipette approach. It was developed to calibrate trapping forces generated by SBAT. Technical aspects of SBAT technology along with these cellular applications will be reviewed in this talk.
5:30 PM - NM10.5.06
Particle Assembly Using Acoustic Holography
Kai Melde 1 , Tian Qiu 1 , Andrew Mark 1 , Peer Fischer 1 2 Show Abstract
1 , Max Planck Institute for Intelligent Systems, Stuttgart Germany, 2 , University of Stuttgart, Stuttgart Germany
Acoustic forces present an attractive way to manipulate particles or droplets in liquids (1). Due to a mismatch of mechanical properties between the suspended particles and the surrounding medium the pressure oscillations of a sound wave give rise to forces, which can be employed for contact-free manipulation. Common techniques are based on acoustic standing waves in resonators or microfluidic channels. Resonance enhances the field amplitude and leads to large forces for pushing, sorting and trapping. Particles are attracted to either (anti-)nodal points, lines or planes. However, the standing wave fields are highly symmetric and depend on the resonator geometry, which typically results in highly symmetric particle assemblies.
Here we present a platform for particle manipulation based on acoustic holograms (2), which enable generation of arbitrary acoustic fields. An acoustic hologram stores a pre-determined wave front (essentially the phase of the complex acoustic field) in the thickness profile of a monolithic plastic plate, which can be fabricated using a conventional 3D printer. When a plane wave passes through the hologram the difference in speed of sound between hologram and medium leads to a spatial modification of the phase. The emitted wave will then diffract and reconstruct the stored acoustic field.
We demonstrate particle assembly and motion. First, we arrange silicone spheres on a surface that is brought into the image plane of a hologram. Other arrangements include assembly at the interface between two liquids or between liquid and air. Furthermore, encoding phase distributions into the field enable perpetual particle motion along pre-defined, close trajectories using static acoustic fields. This simple and low-cost method is generally applicable and new manipulation strategies are presented.
(1) Nilsson, J., Evander, M., Hammarstrom, B. & Laurell, T. Review of cell and particle trapping in microfluidic systems. Anal. Chim. Acta 649, 141-157, doi:10.1016/j.aca.2009.07.017 (2009)
(2) Melde, K., Mark, A. G., Qiu, T. & Fischer, P. Holograms for acoustics. Nature 537, 518-522, doi:10.1038/nature19755 (2016)
5:45 PM - NM10.5.07
Electroformed Three-Dimensional Magnetic Microrobots
George Chatzipirpiridis 1 , Carmela De Marco 1 , Bradley Nelson 1 , Salvador Pane i Vidal 1 Show Abstract
1 Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, ETH Zurich, Zurich Switzerland
Biomedical wireless micro- and nanorobots have been proposed as promising tools to perform minimally invasive procedures such as targeted drug delivery, localized diagnostics, and micro surgery. The main challenge faced by these wireless microsystems is efficient energy transfer and their locomotion in environments such as the human body. Recently, magnetic micro- and nanostructures have been proposed as miniaturized biomedical platforms and their control is achieved by applying magnetic fields generated by external electromagnets. Fabricating such devices with specific magnetic and mechanical properties remains challenging. Electrochemical fabrication has significantly contributed to the development of micro- and nano- machines. Electrochemical processes such as electrodeposition and electroless deposition have been employed to integrate functional or protective coatings on small robotic platforms. For example, Schuerle et al. has shown that magnetic micromachines can be fabricated using helical and tubular phospholipids scaffolds, which can be successfully coated with a magnetic multialloy using electroless deposition. Chitosan-based biofilms have also been electrodeposited on magnetic microrobotic platforms. Likewise, several swimmers have been built on nanowires, nanotubes and other microstructures obtained by template-assisted electrodeposition. This approach has been used to form bio-inspired helical micro- and nano- actuators, named as artificial bacterial flagella (ABFs), which use corkscrew motion induced by external magnetic fields for their locomotion. Hybrid micrometric ABFs can be fabricated using electrodeposition in three-dimensional arrays obtained by two-photon polymerization. Combining template-assisted electrodeposition and dealloying, nanoscale ABFs have been recently reported. Unfortunately, the magnetic volume of ABFs structures is relatively small in comparison to their entire volume since they have only a magnetic coating or a small magnetic head. Fully hard magnetic ABFs would be beneficial in terms of motion control efficiency, overcoming the drag of fluids mimicking viscous body environments. In this paper, we capitalize on an electrochemical technique called electroforming to fabricate microscale ABFs fully made of hard-magnetic material. Electroforming has been previously used to successfully fabricate soft-magnetic tubular microrobots for ophthalmic drug delivery. To electroform the helical microswimmers, a template on a self-curing polymer coated mandrel is created using a laser beam, which ablates precisely the coating, and exposes the mandrel surface. Subsequently, the magnetic material is electrodeposited in the trenches produced by the laser. This result paves the way to the realization of fully hard magnetic untethered microswimmers for in vivo biomedical applications.
NM10.6: Poster Session II: Polymer Nanostructure Materials
Thursday AM, April 20, 2017
Sheraton, Third Level, Phoenix Ballroom
9:00 PM - NM10.6.01
Remote Control of Light-Triggered Oncolytic Virotherapy
Zi-Xian Liao 1 Show Abstract
1 , Institute of Medical Science and Technology, Kaohsiung Taiwan
Clinical virotherapy has been successfully approved for use in cancer treatment by the US Food and Drug Administration (FDA). Among innovative treatments for cancer therapy, oncolytic virotherapy (OV) represents a class of promising cancer therapeutics, with viruses from several families currently being evaluated in clinical trials. Additionally, clinical trials involving adeno-associated virus (AAV)-mediated gene delivery have enabled successful treatment of a number of monogenic disorders and developments in tissue engineering. However, one of the most important technical solutions needed for clinical virotherapy is enhanced systemic virus delivery. Achieving efficacious and accurate systemic delivery will greatly broaden opportunities in OV. Here we show that recombinant AAV serotype 2 (AAV2) chemically conjugated with iron oxide nanoparticles (~5nm) have remarkable ability to be remotely guided under magnetic field. Transduction is achieved with micro-scale precision. Furthermore, a gene for production of the photosensitive protein KillerRed was introduced into the AAV2 genome to enable photo-dynamic therapy (PDT); or light-triggered OV. In vivo experiments revealed that magnetic guidance of “ironized” AAV2-KillerRed injected by tail vein in conjunction with PDT significantly decreases the tumor growth via apoptosis. This proof-of-principle demonstrates guided and highly localized micro-scale, light-triggered OV.
9:00 PM - NM10.6.02
Malav Desai 1 2 3 , Ju Hun Lee 1 3 , Seung-Wuk Lee 1 2 3 Show Abstract
1 Bioengineering, University of California, Berkeley, Berkeley, California, United States, 2 Bioengineering, University of California, San Francisco, San Francisco, California, United States, 3 Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, California, United States
We developed novel protein-based bio-lasers that achieve Whispering Gallery Modes. We designed a transparent protein-based material with a high enough refractive index to confine light through total internal reflection. The resulting materials possess a component capable of stimulated emission to allow for the generation and amplification of coherent light. In order to develop the protein-based lasing materials, we use elastin-like polypeptides (ELP) as the core polymer and green fluorescent protein (GFP) as the stimulated emission component. ELP are elastic proteins composed of the pentapeptide ‘Val-Pro-Gly-Xaa-Gly’ with a guest residue ‘Xaa’ that can be any amino acid other than Pro. ELPs are also thermoresponsive as they remain soluble at low temperatures and phase separate above their transition temperature. We engineered our ELPs with terminal ‘Cys’ residues that can be used for crosslinking with a 4-arm polyethylene glycol/maleimide crosslinker to synthesize hydrogels. In addition, we synthesized ELP/GFP fusion proteins that can be incorporated into these hydrogels. We used the engineered ELP and ELP/GFP fusion proteins to create transparent hydrogel microspheres by crosslinking them in an organic solvent/hexane emulsion. The hydrogels have thermoresponsive swelling, which results in a high protein content and therefore a high refractive index near the physiological temperature of 37°C. Finally, we characterized the fusion proteins, hydrogel microsphere characteristics and thermoresponsive lasing properties of our bio-lasers.
9:00 PM - NM10.6.03
Bio-Based Conducting Hydrogel Nanocomposite Doped with Carbon Nanotubes for Biomedical Application
Jean-Francois Guillet 1 2 , Muriel Golzio 2 , E. Flahaut 2 Show Abstract
1 , Univ Toulouse 3-Paul Sabatier, Toulouse France, 2 , CNRS, Toulouse France
Since the last decade, many research projects have been performed on electrically conducting hydrogel materials that find applications in various fields such as soft robotics, stretchable conductors, and biomedicine. Actually, as nonionic hydrogels are natively electrical insulator, different strategies have to be used to increase their electrical conductivity. Among those, salt doping, incorporation of conducting fillers such as conducting polymers, [1 - 2] or the addition of nanomaterials have been reported. Hence, conducting hydrogels are now commonly used in clinical practice and experimental medicine, for instance in Transdermal Drug Delivery (TDD) technologies, know to improve the quality of life of the patient. Our work focuses on the electroporation method that allows the increase of the skin permeability and the trandermal delivery of large molecules, such as insulin. Here, we report the fabrication of an innovative biomedical device that includes a biocompatible polymer matrix (hydrogel) and double-walled-carbon-nanotubes (DWCNTs) in order to improve both mechanical and electrical properties. This nanocomposite device aims to permeabilize skin and deliver drug molecules at the same time. For such an application, the nanomaterial added in the hydrogel needs to have specific properties such as high electrical conductivity and specific surface area. Carbon nanotubes, and especially DWNTs , are ideal candidates, combining a high electrical conductivity with a very high specific surface area (ca. 1000 m2/g) together with a good biocompatibility when included in a material or deposited on a surface . The preparation of the nanocomposite material as well as our first results of electrostimulated transdermal delivery using an ex vivo mouse skin model will be presented. Moreover, toxicity aspects which have to be considered for such an application are will also be discussed.
 P. Manandhar, P. D. Calvert, J. R. Buck, IEEE Sens. J. 2012, 12, 2052–2061.
[2 ] F. Aouada, M. Guilherme, G. Campese, E. Girotto, A. Rubira, and E. Muniz, Polym. Test. 2006, 25, 158–165.
 E. Flahaut, R. Bacsa, A. Peigney, Ch. Laurent, "Gram-Scale CCVD Synthesis of Double-Walled Carbon Nanotubes", Chem. Commun., (2003), 1442-1443
 A. Béduer, F. Seichepine, E. Flahaut, I. Loubinoux, L. Vaysse, Ch. Vieu, "Elucidation of the role of carbonnanotube patterns on the development of cultured neuronal cells", Langmuir, 28, (50), (2012), 17363 –17371
9:00 PM - NM10.6.04
Biocompatible D–A Semiconducting Polymer Nanoparticle with Light-Harvesting Antenna for Highly Effective Photoacoustic Imaging Guided Photothermal Therapy
Jinfeng Zhang 1 , Chun-Sing Lee 1 Show Abstract
1 , City University of Hong Kong, Hong Kong China
The development of nanotheranostic agents that integrate diagnosis and therapy for effective personalized precision medicine has obtained tremendous attentions in the past few decades. In this report, a biocompatible electron donor-acceptor conjugated semiconducting polymer nanoparticles (PPor-PEG NPs) with light harvesting antenna was prepared and developed for highly effective photoacoustic imaging guided photothermal therapy. To the best of our knowledge, it is the first time that the concept of light harvesting antenna is exploited for enhancing the photoacoustic signal and photo-thermal energy conversion in polymer-based theranostic agent. Combined with the additional merits including donor-acceptor pair to favor electron transfer and fluorescence quenching effect after NP formation, the photothermal conversion efficiency of the PPor-PEG NPs was determined to be 62.3%, which is the highest value among reported polymer NPs. Moreover, the as-prepared PPor-PEG NP not only exhibited a remarkable cell-killing ability but also achieved 100 % tumor elimination, demonstrating its excellent photothermal therapeutic efficacy. Finally, the as-prepared water-dispersible PPor-PEG NPs showed good biocompatibility and biosafety, making them a promising candidate for future clinical applications in cancer theranostics.
9:00 PM - NM10.6.05
Controlling the Amount and Position of Vesicle Fusion with a Bilayer Lipid Membrane Using an Electrostatic Interaction
Azusa Oshima 1 , Koji Sumitomo 2 , Hiroshi Nakashima 1 Show Abstract
1 , NTT Basic Research Laboratories, Atsugi, Kanagawa, Japan, 2 , University of Hyogo, Himeji, Hyogo, Japan
Assay systems that combine membrane proteins and artificial bilayer lipid membranes (BLMs) have been proposed and extensively studied. We previously reported that BLMs suspended over microcavities were stable and that the activity of model proteins such as α-Hemolysin inserted in a BLM could be examined by using a fluorescent indicator. However, determining how to place the membrane proteins in the desired location is a sizable hurdle on the path to device fabrication. In this study, we have tried to control the amount and position of vesicle fusion with supported bilayer lipid membranes (s-BLMs) on a SiO2 substrate by employing an electrostatic interaction, because the vesicle fusion of proteoliposomes with BLMs is a promising way of arranging membrane proteins.
Patches of cationic s-BLMs were prepared by rupturing giant unilamellar vesicles (GUVs), which contained cationic lipids (DPhPC:EDPPC:Cholesterol=8-x:x:2, 0.5 mol% NBD-DOPE). The concentration (x) of the cationic lipids in the GUVs was in the 5-20% range. Large unilamellar vesicles (LUVs) were prepared with anionic lipids (DOPS:DOPC=1:9, 0.5 mol% Rhodamine-DPPE). The anionic LUVs were added to a chamber containing the substrate, and vesicle fusion was investigated using fluorescence microscopy. 30 minutes after the anionic LUVs were added, the patch became slightly larger as a result of vesicle fusion with the anionic LUVs. The rate of increase in the patch size (ΔS/S, where S is the patch area) caused by vesicle fusion was 23.5±11.9% (n=45). The rhodamine fluorescence was limited to the patch, and no fluorescence was observed on the substrate. Under this condition, since the surface of the SiO2 substrate was slightly negatively charged, neither rupture nor adsorption was caused by the electrostatic repulsion with the anionic LUVs. Vesicle fusion occurred selectively only on the cationic s-BLM patch. Since positively charged s-BMLs are neutralized by anionic lipids in fused vesicles, no further fusion occurred. The amount of vesicle fusion could be controlled by controlling the concentration of the cationic lipids in the s-BLMs. We also confirmed that there was sufficient fluidity and continuity of the s-BLMs after anionic LUV fusion by employing fluorescence recovery after photobleaching. These results suggest that we have succeeded in controlling the amount and position of LUV fusion.
Membrane proteins, which are extracted from biological cells, are generally included in liposomes containing DOPS and DOPC. Therefore, negatively charged proteoliposomes are preferable because of their function. Controlling the fusion of negatively charged proteoliposomes will help us to fabricate biomedical nanodevices that work with membrane proteins such as receptors.
9:00 PM - NM10.6.06
Development of Functional Gelatin/Chitosan Films Incorporated with Silica Nanoparticles Formed by Biomimetic Silica Deposition
Mi-Ran Ki 1 2 , Sung Ho Kim 1 , Jong Ki Kim 1 , Ki Baek Yeo 1 , Seung Pil Pack 1 Show Abstract
1 Bioinformatics & Biotechnology, Korea University, Sejong-si Korea (the Republic of), 2 Industrial Technology, Korea University, Sejong-si Korea (the Republic of)
Here, we fabricated a bio-inspired film mimicking natural extracellular matrix (ECM) for bone regeneration including gelatin which is denatured type I collagen and chitosan which provides structural integrity to form stable structures. Gelatin and chitosan were mixed together, and which were set in the wells of 12 well plate and dried. The dried films were immersed into acidic alcohol containing tetraethoxysilane and choline chloride for varying times to induce silica deposition on the surface of films, presenting a spherical morphology with size range of less than 1 µm. The silica-mineralized gelatin/chitosan film maintained the structure without decomposition in cell culture media whereas the gelatin/chitosan film was easily disintegrated in aqueous media. To increase the strength of film, tyramine functionalized gelatin was mixed with caffeic acid-conjugated chitosan and then cross-linked by oxidized diphenol self-polymerization. In the same way mentioned above, silica-mineralization was performed on the cross-linked gelatin/chitosan film. Biological properties of these films were determined using MC3T3-E1 cell line. The silica mineral enhanced both the mRNA levels of BMP2 in early stage and osteocalcin in late in cultures of osteoblasts. Alkaline phosphatase activity and calcium mineral deposition were increased by silica deposition. Hence, this composite shows promise for bone tissue engineering.
9:00 PM - NM10.6.07
Fabrication of Monodisperse Linear Green Fluorescent Protein Oligomers with Defined Valency
Yu-na Kim 1 , Yongwon Jung 1 Show Abstract
1 , KAIST, Daejeon Korea (the Republic of)
Nano-assemblies formed by protein building blocks offer new materials having high biocompatibility, biodegradability and innate stability in water.  But creating precise supramolecular assemblies of functional proteins with defined structures and a controlled number of protein-building blocks is a big challenge. Previously, we reported a series of supramolecular green fluorescent protein (GFP) oligomers that are assembled in precise polygonal geometries.  The circular form of GFP polygon gives geometrical and dimensional rigidity, that may limit wider uses of these GFP polymers with restricted patterns of spatial protein organization. Here we developed a co-expression system for two proteins that are self-assembled in Escherichia coli ( E.coli) to produce linear forms of supramolecular GFP polymers. These oligomers are fully genetically encodable (so fusible to other proteins and produced in cells), suitable for visualization (with its fluorescent nature), and can be isolated in a discrete size. High-valent protein polymers (up to 15-mer) with higher flexibility are more effectively generated in fabrication of linear GFP polymers than in the case of circularly closed GFP polygons. Several functional proteins are displayed on the linear GFP oligomers multivalently and the protein complexes are visualized by a transmission electron microscope. We believe that these structurally varied GFP oligomers would broaden the range of available applications and observable biological events with artificial GFP assemblies.
 Bastings et al., Macrocyclization of enzyme-based supramolecular polymers, Chem. Sci., 2010, 1, 39, 3351-3357
 Kim et al., Green fluorescent protein nanopolygons as monodisperse supramolecular assemblies of functional proteins with defined valency, Nat. Commun., 2015, 6, 7134
9:00 PM - NM10.6.08
ATP Synthesis by Reconstitution of Membrane Proteins Bacteriorhodopsin and ATP-Synthase in Triblock Co-Polymer Vesicles
Satarupa Dhir 1 , Sinoj Abraham 1 , Ehsan Jenab 1 , Carlo Montemagno 1 Show Abstract
1 , University of Alberta, Edmonton, Alberta, Canada
According to International Energy Agency (IEA) report, the energy use in the form of fossil fuels and renewable energy is predicted to rise by 71% from 2012 to 2040 for non-OECD (outside the organization for economic cooperation and development) nation while for OECD nations it would rise by 18%. Economic growth along with infrastructural and transportation development is responsible for this rapid energy demand. Hence, the global energy related carbon dioxide (CO2) emissions are projected to increase by one-third from 2012 to 2014. Consequently, an efficient technology has to be devised for CO2 capture and mitigation.
In this work, we introduce a popular method to reconstruct cellular processes by imitating natural systems. Cells are the major functional units of all living organisms that perform diverse biochemical functions. The energy for many of their vital functions is provided by ATP (Adenosine triphosphate) synthesized in mitochondria or chloroplasts. ATP powers most of the energy-consuming activities of the cell and regulates many biological pathways. The functions of cells can be mimicked through incorporation of membrane proteins and lipid membranes. Conventionally, lipid membranes have been used for the recreation of the natural environment of membrane bound proteins. However, the future applicability of protein-reconstituted lipid membranes is limited due to both chemical and mechanical instability. To create the artificial environment necessary for membrane bound proteins, self-assembled and amphiphilic ABA triblock copolymers have been used as a prospective building material for new biomimetic membranes. Key characteristics of these polymer membranes (polymersomes) such as mechanical stability, membrane flexibility and good assembly make it a better choice over lipid membranes. Poly(dimethyl siloxane) or PDMS based copolymers along with Poly(oxazoline) or PMOXA has been suggested as an alternate to natural lipids. The unique properties of PDMS such as low intermolecular forces, flexibility, high hydrophobicity, and chemical-physical-biological inertness combined with the bio-compatibility of PMOXA makes it excellent for an ABA system.
Few work has been reported on incorporation of two membrane proteins into the polymersomes system. In current case, energy-transducing protein bacteriorhodopsin (bR) along with rotary motor protein F1F0 ATP synthase (ATPase) has been incorporated into PMOXA-PDMS-PMOXA triblock system through solubilization of polymersomes by n-Octyl-β-D-Glucopyranoside. The valuable energy currency “ATP” is generated through coupled activity of proton pumping by bR in presence of light along with conduction of proton through F0 towards F1 for conversion of ADP (Adenosine diphosphate) into ATP. This form ATP generation nano-reactors along with Calvin Cycle enzymes can be used to mimic artificial photosynthesis system so as to capture industrial CO2 emissions and convert it into various value-added biofuels.
9:00 PM - NM10.6.09
A Molecular Dynamics Study of Geometrical and Temperature Effects on Sintering Dynamics of Cu-Ag Core-Shell Two-Nanoparticle Model
Jiaqi Wang 1 , Seungha Shin 1 , Anming Hu 1 Show Abstract
1 , The University of Tennessee, Knoxville, Tennessee, United States
Atomic-level understanding in nanoparticle (NP) sintering dynamics is beneficial for enhancement in properties (i.e., mechanical, thermal or electrical properties) of NP applications, such as conductive films, printable nanoinks and electrode. Because of the difficulty in observing sintering process at atomic scale, molecular dynamics simulations are employed to investigate the sintering of Cu-Ag core-shell two-NP model. Geometry and temperature are two factors examined in this original research. The evolutions of local crystalline orders, shrinkage, potential energy and mean square displacement are tracked to characterize the sintering process. Thus, sintering mechanism involves reorientation, plastic deformation, surface diffusion, wetting and crystallization-amorphization-recrystallization are unraveled. The Cu core is neither coalescent in solid-phase nor in surface-premelting-induced sintering, however, it plays the role of enhancing the mobility of Ag shell atoms, contributing to the sinterability and bonding strength of NPs. Size-dependent optimal core radius/shell thickness ratio is also proposed to achieve maximum densification, and thus maximum bonding strength at room temperature.
9:00 PM - NM10.6.10
Silicon Substrate Patterns on Silane Functionalized Surfaces via Block Copolymer Lithography of Cylinder-Forming Polystyrene-Block-Poly(dimethylsiloxane) Self- and Directed-Assembly
Dipu Borah 1 , Michael Morris 1 Show Abstract
1 Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN) & AMBER Centre, Trinity College Dublin, Dublin Ireland
Polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS) is an ideal block copolymer (BCP) system for self-assembly and inorganic template fabrication because of its high Flory-Huggins parameter (χ ~0.26) at room temperature in comparison to other block copolymers, and high selective etching ability between PS and PDMS block for nanopatterning. Self-assembly in PS-b-PDMS BCP is achieved by combining the hydroxyl-terminated poly(dimethylsiloxane) (PDMS-OH) brush surfaces with solvent annealing. As an alternative to standard brush chemistry, we report here the use of surfaces functionalized with silanes-based self-assembled monolayers (SAMs). A solution-based approach to SAM formation was adopted in this investigation. The influence of the SAM-modified surfaces upon BCP films was compared with polymer brush-based surfaces. The cylinder forming PS-b-PDMS BCP and PDMS-OH polymer brush were synthesized by sequential living anionic polymerization. It was observed that silane SAMs provided the appropriate surface chemistry which, when combined with solvent annealing, led to microphase segregation in the BCP films in which ordered PDMS cylinder arrays in the polymeric PS matrix were obtained. It was also demonstrated that orientation of the PDMS cylinders may be controlled by judicious choice the appropriate silane. The PDMS patterns were successfully used as etching mask to transfer the BCP pattern to underlying silicon substrate by a plasma etched-based with sub-25 nm silicon nanoscale patterns. This SAM/BCP approach to nanopattern formation shows promising results, pertinent in the field of nanotechnology, and with much potential for application, such as in the fabrication of nanoimprint lithography stamps, nanofluidic devices or in narrow and multilevel interconnected lines.
9:00 PM - NM10.6.11
Glucose Oxidase-Mimicking Magnetic Nanochains for Label-Free Colorimetric Biomedical Detection
Peng Wang 2 1 , Hongwei Duan 2 Show Abstract
2 School of Chemical and Biomedical Engineering, Nanyang Technological University, 50 Nanyang Avenue Singapore, 1 Nanyang Environment and Water Research Institute (NEWRI), Interdisciplinary Graduate School, Nanyang Technological University, Singapore Singapore
We report GOx-mimicking magnetic-supported Au nanoparticles (AuNPs)
which can easily be separated and recycled by using high saturation
magnetization. Firstly, Fe3O4/polystyrene-based magnetic nanochains
(MNCs) were prepared by aligning them together in presence of an
external magnetic field, and covalently linking the closely
Fe3O4/polystyrene NPs by self-polymerization of dopamine to form the
polydopamine (PDA) coated MNCs (PMNCs). The PMNCs further
reduce HAuCl4 locally to prepare small and uniform AuNPs loaded on
the surface of PMNCs (PMNCs@AuNPs). The naked AuNPs on the
surface of PMNCs (PMNCs@AuNPs) exhibit GOx-mimicking catalytic
activity which is able to catalytically oxidize glucose in presence of
oxygen to produce gluconate and hydrogen peroxide (H2O2). Interrogated
by horseradish peroxidase (HRP)-based colorimetric assay in presence of
a peroxidase substrate, signals can easily and directly be traced with
naked eye without the need of any complicated analytical instruments.
The catalytic activity of PMNCs@AuNPs remains switch-off when
biomolecules conjugate with AuNPs via gold-sulphur chemistry or
non-covalent interactions leading to inactive surface for catalysis.
However, in absence of any biomolecules, the surface remains free and
GOx mimicking catalytic activity of AuNPs remains switch-on. Moreover,
both PMNCs and PMNCs@AuNPs could readily undergo magnetic
separation, hence easily recyclable, and also can self-stir under a spinning
magnetic field. Therefore, employing these properties, we design a
platform for ultrasmall and self-stir GOx-mimicking PMNCs@AuNPs
biosensor for biomolecule recognition, separation and label-free
colorimetric detection in small volume.
Donglei (Emma) Fan, University of Texas at Austin
Xiaodong Chen, Nanyang Technological University
Peer Fischer, Max Planck Institute for Intelligent Systems
Tony Huang, Duke University
NM10.7: Nanoparticles and Bioapplications I
Thursday AM, April 20, 2017
PCC West, 100 Level, Room 102 AB
9:15 AM - *NM10.7.01
Nanomanufacturing Research at NSF
Khershed Cooper 1 Show Abstract
1 , National Science Foundation, Arlington, Virginia, United States
Since the announcement of the NNI in 2000, nanoscience and nanotechnology research and development has made many advances in understanding physical phenomena at the nano-scale, in developing new nanomaterials and nanodevices and in formulating new measurement and characterization methods. To translate lab-scale discoveries and inventions to the commercial scale, nanomanufacturing research programs have ramped up their activities. At NSF, the Nanomanufacturing (NM) and Scalable Nanomanufacturing (SNM) efforts have received and supported many interesting ideas in addressing nanomanufacturing challenges. This talk will describe these basic research efforts, provide project examples and discuss future opportunities.
9:45 AM - *NM10.7.02
Assembly of Nanoparticles for Tumor Theranostic Applications
Jianfeng Zeng 2 , Xiaju Cheng 2 , Haibin Shi 2 , Zhenyu Gao 1 , Mingyuan Gao 1 Show Abstract
2 Centre for Molecular Imaging and Nuclear Medicine, Soochow University, Suzhou China, 1 Institute of Chemistry, Chinese Academy of Sciences, Beijing China
Towards tumor theranostic applications, different strategies were developed for forming nanoparticles/nanoparticle assemblies in vivo. In this presentation, we will present a few examples on tumor hypoxia-induced assembly of organic/inorganic hybrid nanomaterials, tumor-associated protease induced self-assembly of iron oxide nanoparticles, and light-triggered self-assembly of Au nanoparticles within tumors. Through in situ assembly, the nanomaterials exhibit greatly improved performance for MRI, photoacoustic imaging and even photothermal therapy of cancers. [1-2]
J. Zeng, M. Chen, Y. Wang, L. Wen, Z. Li, Y. Wu, M. Gao, and Z. Chai, Adv. Health. Mater., 2016, 5, 772.
X. Cheng, R. Sun, L. Yin, Z. Chai, H. Shi, and M. Gao, Adv. Mater., 2016, in press.
10:15 AM - NM10.7.03
Scalable Materials Integration into Lipid Multilayer Microarrays for Cell-Based High-Throughput Screening
Aubrey Kusi-Appiah 1 , Troy Lowry 1 , Steven Lenhert 1 Show Abstract
1 , Florida State University, Tallahassee, Florida, United States
High-throughput screening in the pharmaceutical industry currently uses robotic pipetting into microwell plates to screen 10^5-10^6 different compounds for potential therapeutic effects in cell culture models. Miniaturization of this process by encapsulating the different compounds into lipid multilayer microstructures in a surface-based array is being developed to make high-throughput screening widely acceptable and affordable for academic research and personalized medicine applications. The main challenge for this application is in scalable manufacturing of the microarrays with each spot containing one of 10^5-10^6 different materials. For this purpose, we have developed a printing based technique we call "nanointaglio" that is compatible with state of the art microarray technology. Nanointaglio involves the transfer of ink from the recesses of a microstructured stamp to a surface resulting in lipid microstructures of controllable multilayer film thicknesses. Culturing cells on the resulting arrays allows for quantitative dose-response curves, and integration of multiple materials onto the same surface for cell-based microarray screening applications.
 A. E. Kusi-Appiah, N. Vafai, P. J. Cranfill, M. W. Davidson, S. Lenhert, Biomaterials 2012, 33, 4187.
 T. W. Lowry, A. Kusi-Appiah, J. J. Guan, D. H. Van Winkle, M. W. Davidson, S. Lenhert, Advanced Materials Interfaces 2014, 1, 1300127.
 A. E. Kusi-Appiah, T. W. Lowry, E. M. Darrow, K. A. Wilson, B. P. Chadwick, M. W. Davidson, S. Lenhert, Lab Chip 2015, 15, 3397.
10:30 AM - NM10.7.04
Intracellular Delivery via Ultrahigh Throughput Mechanoporation for Cell Therapy Applications
Harish Dixit 1 , Renate Starr 2 , Daniel Nampe 1 , Yanyan Zhang 3 , Christopher Ballas 4 , Hideaki Tsutsui 1 , Christine Brown 2 , Stephen Forman 2 , Masaru Rao 1 Show Abstract
1 , University of California, Riverside, Riverside, California, United States, 2 , City of Hope Beckman Research Institute and Medical Center, Duarte, California, United States, 3 , CGG Veritas, Houston, Texas, United States, 4 , Indiana University School of Medicine, Indianapolis, Indiana, United States
Cancer immunotherapies, or adoptive cell transfer (ACT), have had promising results clinically and show great promise as an alternative to current therapies, such as chemotherapy or radiation. However, the methods used to genetically engineer the anti-cancer functionalities into the required cell type (T lymphocytes) possess certain drawbacks that limit them in automation and cost. There is a critical need for the development of a new cell modification strategy that addresses these shortcomings. Microinjection, which physically creates a transient membrane pore for the delivery of exogenous payloads, may represent one such solution. However, the gold standard of this technology requires significant improvement in order to be competitive against current techniques for genetic modification.
We outline preliminary efforts to develop a new form of microinjection using silicon microfabrication. To simplify fabrication procedures, and demonstrate a proof-of-concept technology, we have created a device for ultrahigh throughput (UHT) cellular manipulation via mechanical membrane poration, i.e. UHT mechanoporation. This technology represents an interim step towards our overall microinjection concept.
The fundamental nature of the device stems from a microelectromechanical systems (MEMS) functional core composed of cell capture sites with monolithically integrated, sub-micrometer scale solid penetrators. Negative flow through aspiration vias at the bottom of the capture sites pulls cells onto the penetrators thus causing membrane poration. Cells are then released by reversing flow through the aspiration vias. The transient nature of membrane disruption enables transfection via diffusion-driven influx of exogenous molecules from the surrounding suspension, while massive parallelization provides for UHT operation (e.g. 10k capture sites in the current device).
Though our original studies validated concept feasibility, low cell treatment efficiencies were observed (~8%). Herein, we describe our recent work on increasing the efficiency of our MEMS-based UHT mechanoporation devices. The implementation of high-resolution fluorescence imaging during device operation and precise flow rate control in the aspiration circuit has provided a means for improved device characterization. Through our efforts, we have been able to increase our efficiencies by optimizing several device parameters. We have
found that improved washing steps, specific flow rates for capture and penetration, and the addition of an immobilization step during our wash cycle significantly improved the proportion of concurrently porated and viable cells in the collected population. These improved parameters thereby increased our cell treatment efficiency nearly 12 fold (~90%). Collectively, such results demonstrate the potential of cellular poration techniques to address limitations in ACT, and have helped to identify directions for future device development.
10:45 AM - NM10.7.06
Immobilization of Functionalized Gold Nanoparticles on Electrode Surfaces Controlled by the Composition of the Electrolyte
Corinna Kaulen 1 , Melanie Homberger 1 , Ulrich Simon 1 Show Abstract
1 , RWTH Aachen University, Aachen Germany
Among nanostructured materials, gold nanoparticles (AuNP) are used successfully in various applications ranging from nanoelectronics, biosensing and theragnostics. In many of these applications, tailor made AuNP are immobilized from aqueous solution onto electrode materials in order to enable electrical addressing or, in the case of biosensensors, specific biomolecule interactions. The controlled immobilization with respect to coverage density and orientation is a crucial step for such applications. In this context we reported on the directed self-assembly of AuNP, which carry either amine- or carboxylic acid terminal groups in their ligand shell, on platinum and gold/palladium alloy electrodes, respectively. We showed that by choosing the appropriate pH and ionic strength selective adsorption on only one electrode type is preferred.
Here we report that the adsorption of the charged AuNP is sensitive to the ion composition present in the electrolyte solution as well. Small, strongly hydrated ions in the electrolyte solution enhance the coverage density on the electrode surface, while large ions with just a weak hydration shell lead to lower covering density. In order to explain the obtained results, we investigated the interactions of monovalent salts MCl (M = Li, Na, K, Cs) with AuNP, functionalized with amine- and carboxylic acid end groups, respectively, as well as with gold and platinum surfaces. As a consequence of these investigations we are able to demonstrate that adopting the electrolyte type and concentration represents an effective parameter to control the assembly and immobilization of functionalized AuNP on electrodes or metal surfaces, in general. As many biomolecules also expose carboxylic acid and amine groups at their surface, our results will help to better control biomolecule-electrode interactions, as well.
 Zhou, W.; Gao, X.; Liu, D.; Chen, X.; Chem. Rev., 2015, 115, 10575−10636.
 Gilles, S.; Winter, S.; Michael, K. E.; Meffert, S. H.; Li, P.; Greben, K.; Simon, U.; Offenhäusser, A.; Mayer, D. Small 2012, 8(21), 3357-3367.
 Kaulen, C.; Homberger, M.; Babajani, N.; Karthäuser, S.; Waser, R.; Simon, U. Langmuir 2014, 30, 574-583.
11:30 AM - *NM10.7.07
Shape-Memory Effects—Soft Materials and Polymers in Small Scale
Andreas Lendlein 1 2 Show Abstract
1 Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow Germany, 2 , University of Potsdam, Potsdam Germany
In recent years substantial progress has been achieved in the synthesis  and characterization  of shape-memory polymers (SMPs). SMPs can be programmed by temporary fixation of a deformation, which is recovered once a suitable stimulus is applied. In most cases, the stimulus is heat, but other stimuli, such as electric current, humidity, light or alternating magnetic fields have been realized as well. Important achievements are remotely controlled actuation and the realization of more complex movements on demand. Suitable polymeric materials that are capable of an SME provide a polymer network architecture consisting of netpoints, chain segments, and molecular switches. Interconnected macroporous rhodium-phosphine coordination polymer network will be presented as artificial soft material, in which shape changes are induced by ultrasonic cavitation based mechanical force. The rhodium(I)-phosphine coordination bonds in the microphase separated pore morphology are acting as molecular switches (temporary cross-links). With two thermal transitions the capability of two subsequent shape changes can be implemented in a polymeric material . Thermally-induced, triple-shape hydrogels will be introduced as soft materials enabling complex movements. Considering the strong trend toward miniaturization in many technical fields, there is a need to evaluate the suitability of SMPs to also serve as enabling technology on the microscale, for example, as fibres, particles,[10, 11] or cuboids.
 K. K. Julich-Gruner, C. Löwenberg, A. T. Neffe , M. Behl , A. Lendlein, Macromol. Chem. Phys. 2013, 214, 527.
 M. Heuchel, T. Sauter, K. Kratz, A. Lendlein, J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 621.
 M. Y. Razzaq, M. Behl, A. Lendlein, Nanoscale 2012, 4, 6181.
 M. Behl, J. Zotzmann, A. Lendlein, Adv. Polym. Sci. 2010, 226, 1.
 P. Zhang, M. Behl, X. Peng, M. Y. Razzaq, A. Lendlein, Macromol. Rapid. Comm, 2016, [E-pub ahead of print on Sept. 26, 2016], DOI: 10.1002/marc.201600439.
 I. Bellin, S. Kelch, R. Langer, A. Lendlein, P. Natl. Acad. Sci. USA, 2006, 103, 18043.
 U. Nöchel, M. Behl, M. Balk, A. Lendlein, ACS Appl. Mater Interf 2016, 8, 28068.
 C. Wischke, A. Lendlein, Langmuir, 2014, 30, 2820.
 Q. Zhang, K. Kratz, A. Lendlein, Polym. Adv. Technol. 2015, 26, 1468.
 F. Friess, U. Nöchel, A. Lendlein, C. Wischke, Adv. Healthc. Mater. 2014, 3, 1986.
 Q. Zhang, T. Sauter, L. Fang, K. Kratz, A. Lendlein, Macromol. Mater. Eng. 2015, 300, 522.
 Y. Liu, M. Y. Razzaq, L. Fang, K. Kratz, A. Lendlein, submitted 2016
12:00 PM - NM10.7.08
Bioimprinting Technology for the Removal of Blood Cancer Cells from Acute Myeloid Leukemia Patients
Vesselin Paunov 1 , Anupam Das 1 , Jevan Medlock 1 , Leigh Madden 2 , David Allsup 3 Show Abstract
1 School of Mathematics and Physical Sciences (Chemistry), University of Hull, Hull United Kingdom, 2 School of Environmental and Life Sciences, University of Hull, Hull United Kingdom, 3 Queens Oncology Centre, Castle Hill Hospital, Cottingham United Kingdom
Biomprinting technology has been recently developed to capture proteins, viruses and entire living cells via their structural and chemical information. Bioimprinting techniques can permanently capture an impression of biological samples into polymer surfaces with promising approaches for early cancer diagnosis , developing selective antimicrobial therapies and formulations [2,3]. Here we report a novel in-vitro approach for the removal of myeloblasts from peripheral blood samples of acute myeloid leukaemia patients utilizing a cell shape recognition technology. Due to size and shape differences between myeloblasts and normal white blood cells, myeloblasts represent an ideal target for bioimprinting. In this work, we have developed the bioimprinting technology to replicate myeloblasts (AML cells) based on their cell shape and size. Myeloblasts were inactivated with fixatives to preserve the cells structural and morphological information. Monolayers of fixed myeloblast cells were prepared by immobilisation on a polyelectrolyte pre-treated glass slides and partially protected by a film of glucose solution. Curable polymer (PDMS) was used to the imprint the exposed part of the cell monolayer and was peeled off after curing. Positive replica of the PDMS bioimrint of AML cell monolayers was prepared and the surface pattern was replicated on a large scale by using roll-to-roll printing on PET foil. These bioimprints were surface modified to promote weak adhesion to the myeloblasts which allow them to be trapped selectively on the surface of the bioimprint based on cell shape recognition. We present the results of our myeloblast cell recognition experiments as a function of the cell concentration and surface coatings of the produced cell imprints. The results indicate that the cell imprinting technology can be used to capture the AML cells based on their shape and size. We demonstrate the selectivity of the cell imprints in retention of the cells of matching shape in a mixture with other cells. The removal of myeloblasts from the normal white blood cells based on interaction with a negative bioimprinted surface which selectively attracts and retains myeloblasts. This technology is expected to find application in AML cell separation devices capable of removing myeloblasts from peripheral blood of AML patients which can lead to new blood cancer therapies.
 K. Ren, N. Banaei, R.N. Zare, ACS Nano, 2013, 7, 6031.
 J. Borovicka, W. J. Metheringham, L.A. Madden, C.D. Walton, S.D. Stoyanov, V.N. Paunov, V.N., J. Am. Chem. Soc., 2013, 135, 5282.
 J. Borovicka, S.D. Stoyanov, V.N. Paunov, Nanoscale, 2013, 5, 8560.
12:15 PM - NM10.7.09
Virus-Templated Single-Walled Carbon Nanotubes for High-Resolution Real-Time Imaging in Ovarian Cancer
Neelkanth Bardhan 1 , Youngjeong Na 2 , Lorenzo Ceppi 2 , Andrew Siegel 1 , Nandini Rajan 1 , Michael Birrer 2 , Angela Belcher 1 Show Abstract
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 , Massachusetts General Hospital, Boston, Massachusetts, United States
Ovarian cancer is one of the most challenging cancers to diagnose and treat, although it is the 7th most common form of cancer in women. The survival rates for women diagnosed with this disease has barely changed since the advent of platinum-based therapies in the past 30 years, with a median 5-year survival < 30% in patients diagnosed with late-stage (Stage III or IV) metastatic ovarian cancer. The standard first step clinical approach to disease management is tumor removal surgery, followed by adjuvant chemotherapy. It has been well documented in the literature that the amount of residual disease remaining after surgery is correlated to the long-term survival of the patients. Therefore, microscopic residual tumor detection during surgery represents a critical challenge in the successful treatment of this disease. Established imaging modalities used in the clinic, such as contrast-enhanced computed tomography (CT), offer poor sensitivity ~ 10% at under centimeter-scale resolution. In this work, we present a first approach utilizing a combination of biotemplated, near-infrared (NIR) fluorescent, targeted nanomolecular probes, along with a custom-designed real-time intraoperative system for image-guided surgical debulking, resulting in enhanced survival. M13 bacteriophage was used as a multifunctional scaffold, to achieve aqueous-dispersed, actively-targeted single-walled carbon nanotubes, as NIR contrast agents for high-resolution real-time imaging during tumor debulking surgery. A targeting peptide against secreted protein, acidic and rich in cysteine (SPARC), which is overexpressed in highly-invasive ovarian cancers, was engineered onto the minor capsid protein, p3, of the virus, to allow for intraperitoneal targeting. We demonstrate that our SWNT-based probe offers sub-millimeter scale resolution, with a very high sensitivity ~ 97% true positive rate, and with acceptable specificity ~ 71%. In an orthotopic ovarian cancer mouse model, using our image-guided surgery we report an enhancement in median survival by 40%, compared to the control group receiving visible eye-only (non-guided) surgery. Taken together, our results provide strong support towards the clinical translation of NIR imaging in guided surgery at the human scale.
12:30 PM - NM10.7.10
A Novel Multifunctional Nanodevice for Targeted Cancer Therapy
Marcus Hoop 1 , Fajer Mushtaq 1 , Christoph Hurter 1 , Xiang-Zhong Chen 1 , Bradley Nelson 1 , Salvador Pane i Vidal 1 Show Abstract
1 , ETH Zurich, Zurich Switzerland
Cancer is one of the leading causes of death globally, hence, the World Health Organization expects up to 19.3 million new cases by 2025.(1) Currently, antineoplastic treatments focus on surgery, chemotherapy, and/or hormone therapy, which cause severe side effects and adversely impact healthy tissue.(2) Current state of the art anticancer agents are administered in high systemic doses, and are not equipped with appropriate target specificity to discriminate cancer from healthy tissues. Research in drug development has focused on improved targeting strategies with monoclonal antibodies.(3) Yet, the therapeutic efficiency of those strategies cannot be further enhanced due to dosage limitations. One of the most promising strategies to overcome these problems is the implementation of advanced functional micro- and nanodevices for enhanced drug delivery.(4) These devices can be precisely maneuvered towards the target area and can be functionalized with various agents for multidrug therapy. Another challenge is related to controlled drug release strategies. On-demand drug release can be achieved by incorporating smart materials that can react in a dynamic way for example to abnormal cellular homeostasis such as pH or temperature.(5) Combining all of the above-mentioned features into one platform remains challenging and has not been achieved, yet.
In our work, we present a new versatile nanodevice for smart drug delivery applications. By template assisted electrodeposition we fabricated nickel-nanotubes with precisely tuned dimensions for magnetic controllability. The inner cavity of the tubes was filled by a drug loaded chitosan hydrogel, which allows for selective drug release in acidic environment present in neoplastic tissue. Furthermore, the geometry of the fabricated nanodevices facilitates exofunctionalization strategies, that allow for enhanced multidrug loading or traceability of the device within the body.
We demonstrate that the ferromagnetic properties of the nanotubes enable controlled propulsion by external magnetic fields. The inner tube cavity is further used to carry a smart drug loaded chitosan hydrogel. In vitro experiments show that this setup allows for controlled drug release depending on the surrounding pH. We were able to demonstrate that our device released significantly more drug at neoplastic tissue conditions of pH 6.0, compared to neutral/physiological conditions (pH 7.4). The outside of the tube was further coated with a gold layer for enhanced biocompatibility and for providing conjugations sites to add either traceability agents or additional drug molecules. This new design represents a multifunctional and smart nano drug carrier for improved cancer therapy.
(1) Baek, S. et al. Nanoscale, 2015, 7, 14191.
(2) Peters, W. A. et al. J. Clin. Oncol., 2000, 18, 1606.
(3) Aggarwal, B. B. et al. Biochem. Pharmacol., 2006, 71, 1397.
(4) Wang, H. et al. Chem. Rev., 2015, 115, 8704.
(5) Mura, S. et al. Nat. Mater., 2013, 12, 991.
NM10.8: Nanoparticles and Bioapplications II
Thursday PM, April 20, 2017
PCC West, 100 Level, Room 102 AB
2:30 PM - *NM10.8.01
Discerning Rare Disease Biomarkers by Micro- and Nanotechnologies
Jeff Tza-Huei Wang 1 Show Abstract
1 , Johns Hopkins University, Baltimore, Maryland, United States
Genomic analysis of biomarkers, including genetic markers such as point mutations and epigenetic markers such as DNA methylation, has become a central theme in modern disease diagnosis and prognosis. Recently there is an increasing interest in using confocal single-molecule spectroscopy (SMS) for genomic detection. The driving force not only comes from its ultrahigh sensitivity that allows detection of low-abundance nucleic acids without the need for amplification but also from its potential in achieving high-accuracy quantification of rare targets via single-molecule sorting. Semiconductor quantum dots (QDs) also show a great promise for biomarker analysis. The unique photophysical properties of semiconductor quantum dots (QDs) such as high quantum yield and photostability make them ideal for use as spectral labels and luminescent probes. QDs also make excellent donors to pair with organic dyes in the fluorescence resonance energy transfer (FRET) process due to the features of narrow emission spectra and small Stokes shift. This enables FRET with minimal direct acceptor excitation and donor-acceptor crosstalk, thereby permitting the design of FRET molecular sensors with extremely low intrinsic fluorescence backgrounds necessary for detecting biomolecular targets at low abundance. On the other hand, microfluidic technologies offer an exciting opportunity to realize the use of biomarkers in routine clinical settings via the development of miniaturized diagnostic systems. These platforms may function as portable bench-top environments that dramatically shorten the transition of a bench-top assay into a point-of-care format. We have developed highly sensitive, quantitative and clinically relevant technologies for analysis of genomic markers based on the convergence of SMS, microfluidic manipulations, and quantum dots. Extraordinary performances of these new technologies have been exemplified by analysis of a variety of biomarkers including point mutations, DNA integrity and DNA methylation in clinical samples.
3:00 PM - *NM10.8.02
Assembling Plasmonic Nanobiosensors for Biomolecular and Cellular Analysis
Young Geun Park 1 , Katsuo Kurabayashi 1 Show Abstract
1 , University of Michigan, Ann Arbor, Michigan, United States
Recent advances in nanomaterials and nanofabrication have brought plasmonic nanobiosensing technologies that show great promise in achieving fast, real-time label-free detection of biomolecular species. This talk summarizes our recent study developing new metrological techniques that incorporate plasmonic nanobiosensors for imaging-based multiplexed protein assay. Our study aims at the translation of plasmonic nanobiosensing to clinical applications as well as fundamental single-cell study. The biosensors for clinical diagnostics are based on arrayed gold nanorod ensemble structures constructed by a scalable microfluidic channel patterning technique. “Nanoplasmonic biosensor antenna,” each consisting of a synthetic nucleic acid-linked nanoantenna structures, are synthesized for single-cell protein secretion measurement.
3:30 PM - NM10.8.03
Artificial Nanostructures for Multifunctional Sensing Devices
Aswini Pradhan 1 , Bo Xiao 1 Show Abstract
1 , Norfolk State University, Norfolk, Virginia, United States
The development and implementation of nanotechnology for biomedical diagnostics and sensing applications have tremendous societal impact. These research directions represent leading edges of the fast-moving development in nanotechnologies with strong insight into the understanding of both fundamental and applied aspects of nanoscience and nanotechnology. We would discuss how nanotechnology has made a tremendous impact, especially in the field of health care. The artificially engineered nanostructures are becoming extremely important due to intricate interplay of light and matter, and produce many useful sensing and energy devices. In that regard, can we make very cost-effective, high throughput nano devices for visual identification of diseases for early stage prevention? We have demonstrated that light transmitted through a nanostructured metal thin film without any apertures can be significantly enhanced. The sensitivity of the resonances to the surrounding medium and the transmission efficiency demonstrate its use for imaging, optical processing, sensing, and point-of-care diagnostic applications. We will discuss the effects of plasmon coupling with the Fano resonances, which enhances the detection sensitivity. We will discuss a cost effective way for the mass production of such diagnostic tools, which may significantly impact the health care for the point-of-care diagnostics. We would also discuss highly aligned self-assembled nanostructures for effective chemical sensing.
This work is supported by NSF CREST.
3:45 PM - NM10.8.04
Phage Nanofiber Based Structural Color Biosensor and Their Pattern Recognition Sensing Network System
Ju Hun Lee 1 2 , Seung-Wuk Lee 1 2 Show Abstract
1 Bioengineering, University of California, Berkeley, Berkeley, California, United States, 2 Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, California, United States
We developed a novel sensitive and selective color sensor that utilizes cross-reactive M13 phage structural array matrices and an accompanying smartphone-based sensing system. Specifically, we developed structural color matrices using M13 phage self-assembled nanostructures. We genetically engineered multiple distinct functional groups on the phage major coat proteins.