Symposium Organizers
Eva Hemmer, University of Ottawa
Niko Hildebrandt, Université de Paris Sud
Jianghong Rao, Stanford University School of Medicine
Fiorenzo Vetrone, University of Quebec-Instutitut National de la Recherche Scientifique
Symposium Support
ACS Nano | ACS Publications
ACS Photonics | ACS Publications
MilliporeSigma (Sigma-Aldrich Materials Science)
Photon etc
NM07.01: Organic Nanostructures and Biopolymers
Session Chairs
Tuesday PM, November 28, 2017
Hynes, Level 3, Room 308
8:30 AM - NM07.01.01
Nanoparticle Assemblies for Cancer Nanomedicine Based on a Cellulose Acetate Platform
Berney Peng 1 , Shajesh Palantavida 2 3 , Saquib Ahmed Peerzade 1 , Maxim Dokukin 2 , Igor Sokolov 2 1 4
1 Biomedical Engineering, Tufts University, Medford, Massachusetts, United States, 2 Mechanical Engineering, Tufts University, Medford, Massachusetts, United States, 3 Center for Nano and Material Science, Jain University, Ramanagaram, Bangalore, India, 4 Physics, Tufts University, Medford, Massachusetts, United States
Show AbstractNanoparticle drug delivery and bio-imaging contrast agents have garnered significant scientific interest in the past two decades. Targeted fluorescent contrast agents can label intra- and extracellular biomarkers while informing clinical diagnostic decisions based on high resolution, real-time optical imaging. Nanoparticles based on natural biopolymers and their derivatives are relatively new and untapped candidates for such applications. A renewable material such as cellulose possesses high potential as a translational nanomaterial due to its biocompatibility and excellent physical properties. Here, we present a cellulose acetate derived fluorescent nanoparticle platform for utility in nanomedicine and demonstrate proof-of-concept synthesis, encapsulation, surface biofunctionalization, and ultimately, in vivo targeting of cancer.
8:45 AM - NM07.01.02
Triplet Fusion Upconversion Enhancement via Dimerization
Dan Congreve 1 , Andrew Pun 2 , Mahesh Gangishetty 1 , Luis Campos 2
1 , Rowland Institute at Harvard, Cambridge, Massachusetts, United States, 2 , Columbia University, New York, New York, United States
Show AbstractUpconversion, the process of converting two low energy photons into one high energy photon, shows great promise for biological imaging due to its tunable NIR excitation, flexible visible emission, and reverse Stokes shift leading to a greatly enhanced signal to noise ratio. The process requires two species: a sensitizer to generate triplets (typically a colloidal nanocrystal or molecular phosphor) and an annihilator to fuse the triplets and generate a high energy photon. Recently, great progress has been made in sensitizer development, as a wide variety of nanocrystals and phosphors have been shown to operate successfully in the NIR. The annihilator, on the other hand, has seen little improvement. Here, we demonstrate a new series of dimerized annihilators that show strong performance enhancements and open the door to triplet fusion upconversion as a strong platform for interacting with biological samples.
We synthesize a series of tetracene-based dimers for use as the annihilator. As compared with the widely used annihilator rubrene, the dimers demonstrate a strong upconversion enhancement across a wide variety of conditions, particularly at low concentrations. Further, the threshold for maximum quantum yield is reduced by a factor of five when compared to rubrene, reducing the excitation power requirements. Transient studies demonstrate that this improvement stems from a threefold enhancement in the upconversion photoluminescence lifetime. The greatly improved emission, robustness in the face of non-ideal environments, and strong reduction in required incident power marks these dimers as strong candidates for future NIR bio-imaging systems.
9:00 AM - *NM07.01.03
Organic Nanoparticles for Sensing, Imaging and Therapy
Bin Liu 1
1 , National University of Singapore, Singapore Singapore
Show AbstractThere is an increasing trend of using organic nanoparticles and especially light-harvesting conjugated polymer nanoparticles as active materials for sensing, imaging and therapy applications. The recent results show that conjugated polymer nanoparticles could be fabricated to have tunable sizes and emission, with over 10-fold brightness as compared to inorganic quantum dots with a similar dimension. In addition, their large absorption cross-sections have also enabled them to be used as photoacoustic contrast agents and for photothermal and photo dynamic therapy. In this talk, I will discuss different strategies to form water-dispersible conjugated polymer nanoparticles and their applications as signal reporters or signal amplifiers for chemical and biological sensing/imaging and therapy.[1] In addition, I will also briefly introduce our recent progress in organic nanoparticles with aggregation-induced emission features as replacement for quantum dots in various applications.[2]
References:
[1] Kai Li and Bin Liu. Polymer-encapsulated Organic Nanoparticles for Fluorescence and Photoacoustic Imaging. Chem. Soc. Rev. 2014, 43, 6570-6597.
[2] Dan Ding Kai Li, Bin Liu* and Benzhong Tang*, Bioprobes Based on AIE Fluorogens, Acc. Chem. Res., 2013, 46, 2441-2453.
9:30 AM - NM07.01.04
Synthesis and In Vivo Investigation of Multifunctional PCLGCIR820 Nanoparticles for Dual Laser Photothermal Therapy
Mukti Vats 1 , Gayathri Chandran 2 , Abhijit De 2 , Rohit Srivastava 3 , Piyush Kumar 3
1 BSBE, Indian Institute of Technology Bombay, Mumbai India, 2 , ACTREC, Maharashtra India, 3 , Indian Institute of Technology Bombay, Bombay India
Show AbstractThe synthesis and development of novel polymers and their use for nanoparticle (NP) synthesis have been an important focus of materials science research in the past decade. NPs delivery systems are useful for in vivo applications because their small size (upto100 nm) allows them to escape reticuloendothelial system (RES) uptake, resulting in prolonged plasma circulation times. These nanocarriers are able to stabilize and protect their cargo from degradation, including drugs and organic dyes. Thermal therapeutics are superior to conventional techniques, as they are minimally invasive and easy to comply, with a great capacity to treat tumors entrenched in vital regions where surgical resection is not possible. Recently, photothermal therapy (PTT) has attracted tremendous attention because of its high efficacy in tumor ablation and minimal damage to normal tissues. Numerous cyanine derivatives have been synthesized as NIR dyes that are mainly utilized in fluorescent imaging during recent years. IR820 dye is one of the most commonly employed medical imaging dyes and approved by US Food and Drug Administration (FDA) for clinical use on patients, which has been widely investigated for photothermal cancer therapy. To sufficiently utilize NIR dyes, various nanocarriers containing NIR dyes have been designed as photo-thermal nano agents. This study is aimed to explore the efficacy of PCLGC nanoparticles as a carrier for IR820 dye targeting development of a cost-effective photo-thermal agent for cancer therapy. GC has been widely used for the delivery of DNA, anti-cancer agents, and dyes. Since the price of photo-thermal therapy should be evaluated for its ability to eradicate cancer in a cost-effective manner, PCLGCIR820 is aimed to offer a cheaper alternative to gold nanoparticles for photothermal studies aiming at tumor resection. As our lab group has recently reported the in-vitro efficacy, we aim to investigate the in vivo photothermal efficiency on cancer mouse models. Our lab group has successfully demonstrated and published formulated multifunctional PCLGC–IR composite nanoparticles for bioimaging and therapy. It Includes the significance of the IR 820 interaction with a PCLGC–IR nano formulation, confirmed by DSC, XRD and dual laser (750 nm and 808 nm) for the first time. In addition to this, stability and degradation studies have been carried out for the first time using LCMS. Further, the in-vitro cytotoxicity of the PCLGC–IR composite nanoparticles was evaluated using NIH3T3 cells. Cellular uptake and PTT studies were per- formed on MDA-MB-231 cells. Thus, this study aims to further explore the invivo photothermal efficacy of the composite PCLGCIR820 nanoagent on murine cancer models with the help of the 3D modeling technique to provide a cutting edge analysis to the invivo studies.
10:15 AM - *NM07.01.05
Self-Assembled Supramolecular Nanosystems for Smart Diagnosis and Targeted Therapy of Intractable Diseases
Kazunori Kataoka 1 2
1 , Univ of Tokyo, Kawasaki Japan, 2 Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, Kawasaki, Kanagawa, Japan
Show AbstractNanotechnology-based medicine (Nanomedicine) has received progressive interest for the treatment of intractable diseases, such as cancer, as well as for the non-invasive diagnosis through various imaging modalities. Engineered polymeric nanosystems with smart functions play a key role in nanomedicine as drug carriers, gene vectors, and imaging probes. This presentation focuses present status and future trends of self-assembled nanosystems from block copolymers for the therapy and the non-invasive diagnosis of intractable cancer.
Nanosystems with 10 to 100 nm in size can be prepared by programmed self-assembly of block copolymers in aqueous entity. Most typical example is polymeric micelles with distinctive core-shell architecture. Compared with conventional formulations, such as liposomes, polymeric micelles have several advantages, including controlled drug release, tissue penetrating ability and reduced toxicity1,2. Notable anti-tumor efficacy against intractable and metastatic cancer, including pancreatic cancer3, glioblastoma4,5, and cancer stem cells6, of antitumor drug-incorporated polymeric micelles with pH- and/or redox potential responding properties was demonstrated, emphasize their promising utility in cancer treatment. Versatility in drug incorporation is another feasibility of polymeric micelles. Loading of imaging reagents makes polymeric micelles with theranostic functions7. These results demonstrate the promising features of polymeric micelles as platform nanosystems for molecular therapy of various intractable diseases.
H. Cabral, K. Kataoka, J. Contrl. Rel. 190, 70 (2014).
Y. Matsumoto, et al, Nature Nanotech. 11, 533 (2016).
H. Cabral, et al, ACS Nano 9, 4957 (2015).
K. Katsushima, et al, Nature Commun. 7, 13616 (2016).
S. Quader, et al, J. Contrl. Rel. 258, 56 (2017).
H. Kinoh, et al, ACS Nano 10, 5643 (2016).
P. Mi, et al, Nature Nanotech. 11, 724 (2016).
10:45 AM - NM07.01.06
Core/Shell Semiconductor Nanocrystals Towards Biomedical Applications
Lihong Jing 1 3 , Kershaw Stephen 2 , Ana Jaklenec 3 , Robert Langer 3 , Andrey Rogach 2 , Mingyuan Gao 1
1 Institute of Chemistry, Chinese Academy of Sciences, Beijing China, 3 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 Department of Physics and Materials Science & Centre for Functional Photonics, City University of Hong Kong, Kowloon Hong Kong
Show AbstractGoverned by the quantum confinement effect, semiconductor nanocrystals (NCs) exhibit unique optical properties such as narrow, relatively symmetric, and particle size-/composition dependent fluorescence ranging from the UV-blue to the mid-IR. This highly attractive flexibility has triggered extensive and detailed exploration of their applications in various and diverse areas including the commercially and societally important biomedical and optoelectronic fields. In particular, construction of semiconductor/semiconductor core/shell structures has been demonstrated to be one of the most effective ways to improve the photoluminescence (PL) efficiency and tune the PL emission of QDs as well. In this abstract, basic chemistry concepts will be introduced for synthesis of highly Fluorescent core/shell type I-VI and I-III-VI-based semiconductor nanocrystals and associated multifunctional nanomaterials; then experimental and theoretical investigations of electronic and optical properties of above nanomaterials; followed with construction of paramagnetically engineered core/shell QDs for buildup of multimodal molecular imaging probes; and as last, biomedical applications of heavy-metal free NIR fluorescent nanocrystals will be focused on.
11:00 AM - *NM07.01.07
Engineering Hierarchical Structures with Biopolymers—Controlling Dimensions from the Nano- to the Macroscale
Fiorenzo Omenetto 1
1 , Tufts University, Medford, Massachusetts, United States
Show AbstractBiopolymers, and structural proteins specifically, are interesting building blocks to engineer materials that recapitulate natural function and performance. The dynamics of molecular self-assembly are at the core of the assembly of materials found in Nature, and result in functional materials that have unique properties like stiffness, toughness, and unusual functionality, all accompanied by structural hierarchy covering dimensions that span from nano- to the macro- scale. The library of such biomaterials include extracellular matrices, nacre, bone, and fibers, all of which possess a heterogeneous, multidimensional structure.
These architectures have been a source of inspiration for fabrication of synthetic counterparts that attempt to mimic their structure and function. The realization of these materials, however, poses a manufacturing challenge given the difficulty of being able to simultaneously control assembly and structure-function properties over such a wide range of dimensional scales: often, control at the molecular level imposes limitations on the control available at larger scales (and vice versa).
In this talk we will review approaches of combining top-down and bottom-up fabrication techniques to engineer hierarchical structures at multiple length scales (at nano-, micro-, and macro-sizes), focusing on silk fibroin as our primary biomaterial. The generation of structures with multidimensional control provides an interesting research avenue where structure-function can be designed and explored in new ways. Additionally, the opportunity and ease of doping of such structures may lead to a new class of designer structures with predefined functions and integration at the interface of technology and biology.
NM07.02: Group IV—Element-Based Bioprobes I
Session Chairs
Tuesday PM, November 28, 2017
Hynes, Level 3, Room 308
11:30 AM - NM07.02.01
New Ways in Nanomedicine Based on Biocompatible Porous Silicon Nanostructures
Vladimir Sivakov 1 , Liubov Osminkina 2
1 , Leibniz Institute of Photonic Technology, Jena Germany, 2 , Lomonosov Moscow State, Moscow Russian Federation
Show AbstractCreation of one-dimensional nanostructures has opened up a new area for device applications in electronics, optoelectronics, thermoelectronics, photocatalysis, photovoltaics, sensor, and bio-imaging. Cancer diagnostic and therapy challenge the scientific community to design research addressing the urgency of ending cancer. I intend here to carry out an ambitious topic including development and in vitro testing of biocompatible silicon-based nanostructures for cancer therapy and diagnostics. These nanostructures will be based on insights gained during the last 5 to 10 years of research and are expected to lead to significant progress steps, by which such material will be promoted from “promising material” to effective material for the bio-photonic and bio-medical applications. Significant expectations are now related to novel classes of inorganic materials such as nanocrystals, NPs, and nanowires, which could exhibit more stable and promising characteristics for both medical diagnostics and therapy. For all these reasons new labelling and drug delivery agents for bio-application are an important field of research with a growing potential for medical use. Si-based nanomaterials (silicon nanowires (SiNWs), porous silicon nanoparticles (SiNPs)) are a type of novel bionanomaterials with attractive properties including excellent electronic and mechanical properties, favourable biocompatibility, huge surface-to-volume ratios, surface tailorability, improved multi-functionality, as well as their compatibility with conventional Si technology. The multi-modal bioimaging of silicon nanoparticles in living cell will be presented and discussed in details. The novel ways in cancer, bacteria and viruses therapy using ultrasound and radio-frequency irradiation will be presented.
11:45 AM - NM07.02.02
Fluorescent Silicon Nanoparticle-Based Bioimaging
Yuanyuan Su 1
1 Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Jiangsu China
Show AbstractInstitute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China
The last twenty years have witnessed rapid advancement of fabricating silicon nanomaterials and vast development of silicon nanomaterials-based applications, including in electronics, energy, environment, biology and biomedicine fields [1]. Fluorescent silicon nanoparticles (SiNPs) attract considerable attention owing to their intrinsic advantages, including relatively strong fluorescence coupled with robust photostability, rich resource support and relatively low cost, industrial maturity, and good biocompatibility[2, 3].
Compared to well-established fluorescent proteins/organic dyes-based bioprobes of severe photobleaching property and II-VI fluorescent quantum dots (QDs)-based nanoprobes involving heavy metal-induced safety concerns, SiNPs feature strong fluorescence, robust photostability, and excellent biocompatibility. Those attractive merits have triggered extensive exploration of SiNPs as potentially ideal biological fluorescent probes [1-4]. Particularly, the cyclic peptides containing the arginine-glycine-aspartic acid sequence (c(RDGyC)) was employed for modifying the SiNPs to produce a kind of peptide-conjugated SiNPs (defined as SiNPs-RGD), which simultaneously featured small size (<10 nm), robust and high fluorescence (photoluminescence quantum yield (PLQY) ≈ 28%), and desirable biological functionality (targeting tumor-associated receptor-αvβ3 integrin) [5]. Furthermore, such resultant SiNPs bioprobes are demonstrated to be superbly suitable for real-time immunofluorescence imaging of cancer cells.
[1] Silicon Nano-biotechnology, ISBN 978-3-642-54667-9, 2014, Publishing company: Springer, Chief-editor: Yao He; Associate editor: Yuanyuan Su
[2] Yuanyuan Su, Xiaoyuan Ji, Yao He. Adv. Mater. 2016, 28, 10567-10574.
[3] Fei Peng, Yuanyuan Su, Yiling Zhong, Shuit-Tong Lee, Yao He. Acc. Chem. Res. 2014, 47, 612-623.
[4] Sicong Wu, Yiling Zhong, Yanfeng Zhou, Bin Song, Binbin Chu, Xxiaoyuan Ji, Yanyan Wu, Yuanyuan Su, Yao He. J. Am. Chem. Soc. 2015, 137, 14726.
[5] Chongxi Song, Yiling Zhong, Xiangxu Jiang, Fei Peng, Yimei Lu, Xiaoyuan Ji, Yuanyuan Su, Yao He. Anal. Chem. 2015, 87, 6718.
NM07.03: Group IV—Element-Based Bioprobes II
Session Chairs
Niko Hildebrandt
Fiorenzo Vetrone
Tuesday PM, November 28, 2017
Hynes, Level 3, Room 308
1:30 PM - NM07.03.01
Synthesis and Characterization of Fluorescent Silica Nanoparticles with Controlled Numbers of Fluorophores
Teresa Kao 1 , Emile Drijvers 1 2 , Ferdinand Kohle 1 , Kai Ma 1 , Tangi Aubert 1 2 , Ulrich Wiesner 1
1 , Cornell University, Ithaca, New York, United States, 2 , Ghent University, Ghent Belgium
Show AbstractSilica chemistry provides a uniquely tunable platform for nanoparticle synthesis, where particle size, nanoscale morphology, and surface properties can be precisely controlled. In the past decade, syntheses have been developed to enable access to ultra-small and monodisperse silica nanoparticles in aqueous media, making such materials ideal candidates as probes for biological imaging. Building on previous studies of amino-acid catalyzed growth of silica nanoparticles, we have synthesized a set of highly fluorescent silica nanoparticle probes with sizes < 40 nm and well-controlled numbers of organic fluorophores/particle and have characterized these materials using both ensemble and single-particle imaging techniques. In addition, we have investigated the role of the amino acid in post-synthesis surface modifications. This work highlights important considerations in the development of probes designed for single-particle fluorescence imaging and sensing applications, where heterogeneities across the nanoparticle ensemble are critical factors in probe performance.
1:45 PM - NM07.03.02
Porous Silicon Optical Biosensor for a Selective Detection of Bacteria Using Lytic Enzymes
Jonathan Rasson 1 , Catherine Nannan 2 , Jacques Mahillon 2 , Laurent Francis 1
1 Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve Belgium, 2 Laboratory of Food and Environmental Microbiology, Université catholique de Louvain, Louvain-la-Neuve Belgium
Show AbstractIn this work we developed and tested a porous silicon (PSi) optical bacteria sensor that allows a label-free and selective detection of bacteria without relying on a biorecognition layer. The working principle of the sensor is as follows: an aqueous solution containing bacteria is flown over a PSi sensor in a transparent fluidic cell to allow the adsorption of bacteria on the surface. Lytic enzymes are then brought in contact with the sensor to selectively lyse the bacteria of interest, Staphylococcus epidermidis, which allows the lysate to penetrate inside the pores. The adsorption and lysis are optically detected using Reflective Interferometric Fourier Transform Spectroscopy (RIFTS) [1] by monitoring the change in intensity of the resulting peak, due to the light scattering by the bacteria, and its shift in position, for the change in optical index induced by the lysate penetration. S. epidermidis cells can thus be detected among other cells, by measuring the shift provoked by their lysis and comparing it to the baseline obtained during a buffer wash after the incubation.
Our selectivity mean, brought in situ during the detection, differs from most bacteria sensors relying on complex and time consuming functionalization schemes, which need to be applied beforehand, to modify the surface chemistry of the sensor to bind expensive recognition elements (antibodies, aptamers,…) [2]. This externally brought selectivity allows the fabrication of a highly versatile sensor that can be used for many applications. Indeed, it can be applied to any species or subspecies of bacteria having a corresponding lytic enzyme, phage or antibiotic that targets their cells specifically.
Secondly, contrary to traditional PSi bacteria sensors, aiming for a whole cell detection, that monitor only the intensity of the RIFTS peak, our sensor benefits from the use of the large reactive internal surface of PSi by monitoring the shift in position of the peak.
Additionally, the use of a novel stabilization method of the PSi in aqueous buffer using an atomic layer deposited oxide layer (either Al2O3 or HfO2) allows us to decrease the noise of the measurements by a factor 10 and thus significantly reduces the signal-to-noise ratio compared to the standard oxidation method [3].
Finally, simple strategies to improve the non-specific binding of cells on the sensor’s surface are currently investigated to help reduce the limit of detection to the lowest level reported in the literature.
With this work, we thus aim at developing a quick and simple platform for the detection of bacteria in aqueous media that ultimately could be used for various applications such as environmental monitoring and food security at multiple points in the food chain or even as a point-of-care platform for simple biological fluids.
[1] C. Pacholski et al., J. Am. Chem. Soc., 127, 11636 (2005).
[2] K. Urmann et al., Analyst, 141, 5432 (2016).
[3] G. Shtenberg et al., ACS Appl. Mater. Interfaces, 6, 16049 (2014).
2:00 PM - NM07.03.03
FRET Based Ultrabright Nanosensors
Saquib Ahmed Peerzade 1 , Igor Sokolov 1
1 , Tufts University, Medford, Massachusetts, United States
Show AbstractMesoporous silica particles provide a novel platform for development of highly fluorescent contrast agents and novel optical sensors. One of the advantages of this platform is the ease of coupling FRET-pair dyes by physical encapsulation inside the particles. Here we present the use of this approach to demonstrate assembly of pH and temperature sensors. Highly sensitive pH sensors are helpful for differentiating cancerous from normal tissues. Ultrabright magnetic temperature sensors can be used to measure and control the temperature in magnetic hyperthermia treatment of cancer. FRET pairs of temperature sensing and reference dyes are physically encapsulated in silica matrix. Similarly, FRET pairs of pH sensitive and non-pH sensitive dyes are used for sensing pH. pH sensor is build in the way it increases its fluorescence with the decrease of pH (this is highly desirable though hard to make property for pH sensors of cancer). Fluorescence in the blue region is observed to increase with the increase in acidity. Further, we demonstrate conjugation of ultrabright sensors with cancer targeting agent (folic acid) and PEG groups.
2:15 PM - NM07.03.04
Near-Infrared Carbon Nanotube Fluorescence—Super-Resolution Imaging for DNA Walker Studies
Jing Pan 1 , Jong Hyun Choi 1
1 , Purdue University, West Lafayette, Indiana, United States
Show AbstractThe unique physical properties of single-walled carbon nanotubes (SWCNTs) have been exploited in novel applications in various fields including electronics and life sciences. Their photoluminescence in the near-infrared (NIR) range, where optical interference from biological tissues is minimum, has rendered them particularly attractive as optical probes in biological environments. Using the NIR fluorescence of SWCNTs, we introduce an integrated super-resolved fluorescence microscopy approach that is capable of long-term imaging to probe the structure and detailed kinetics of synthetic molecular motors from DNA, the so-called DNA walkers. DNA walkers, inspired by remarkable molecular machineries of intracellular protein motors like kinesins and dyneins, make stepwise movements along prescribed tracks by converting chemical energy into mechanical motion through a series of conformation changes. Our subdiffraction tracking and imaging in the visible and second near-infrared spectra resolve walker structure and reaction rates. The distributions of walker kinetics are analyzed using a stochastic model to reveal reaction randomness and the rate-limiting biochemical reaction steps. The visible/near-infrared subdiffraction microscopy developed in this work should be valuable to not only the field of DNA nanotechnology, but also optical imaging in biology and biomedicine.
2:30 PM - NM07.03.05
Fluorescent Single-Walled Carbon Nanotubes for Protein Sensing
Gili Bisker 1
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Show AbstractThe ability to specifically and selectively recognize, detect, and monitor molecules of interest is essential for many biomedical applications, and is a crucial element in innumerable biological and chemical processes. Recently, a new concept for generating synthetic recognition sites was introduced, namely, Corona Phase Molecular Recognition (CoPhMoRe). In this approach, a heteropolymer is adsorbed onto the surface of an optically active nanoparticle, forming a structured 3-dimensional corona around it, such that it can selectively and specifically recognize a target molecule. The adsorbed polymer does not necessarily have any affinity towards the target analyte, but rather its pinned configuration when folded onto the particle scaffold forms a recognition site. This generic scheme has been demonstrated using fluorescent single walled carbon nanotubes (SWCNTs) as the underlying nanoparticles for optical signal transduction, monitoring spectral response of their fluorescence emission to reveal analyte adsorption onto the SWCNT corona. Initial demonstrations of SWCNT based CoPhMoRe include corona phases selective towards small molecules. In this talk, I will describe the first protein-targeted CoPhMoRe, where a phospholipid-PEG corona is shown to render the SWCNT a sensor for fibrinogen, the building block of blood clots. The fibrinogen recognition also occurs in serum environment, at the clinically relevant fibrinogen concentrations in the human blood. These results open new avenues for synthetic, non-biological antibody analogues that recognize biological macromolecules, and hold great promise for medical and clinical applications.
2:45 PM - NM07.03.06
Nanocarbon In Vivo Optical Implantable/Wearable Biosensors for Cancer
Daniel Heller 1 2 , Jackson Harvey 1 2 , Prakrit Jena 1 , Hanan Baker 1 2 , Gul Zerze 3 , Ryan Williams 1 , Thomas Galassi 1 2 , Daniel Roxbury 4 , Jeetain Mittal 3
1 , Memorial Sloan-Kettering Cancer Center, New York, New York, United States, 2 , Weill Cornell Medical College, Cornell University, New York, New York, United States, 3 , Lehigh University, Bethlehem, Pennsylvania, United States, 4 , University of Rhode Island, Kingston, Rhode Island, United States
Show AbstractThe real-time and spatially-resolved detection and identification of analytes in biological media present important goals for next-generation nanoscale probes and sensors. MicroRNAs and other small oligonucleotides in biofluids are promising disease biomarkers, yet conventional assays require complex processing steps that are unsuitable for point-of-care testing or for implantable or wearable sensors. To this end, we employ the intrinsic near-infrared fluorescence of single-walled carbon nanotubes which is photostable yet sensitive to the immediate environment. Here, we report an engineered carbon-nanotube-based sensor capable of real-time optical quantification of hybridization events of microRNA and other oligonucleotides. The mechanism of the sensor arises from competitive effects between displacement of both oligonucleotide charge groups and water from the nanotube surface, which result in a solvatochromism-like response. The sensor, which allows for detection via single-molecule sensor elements and for multiplexing by using multiple nanotube chiralities, can monitor toehold-based strand-displacement events, which reverse the sensor response and regenerate the sensor complex. We also show that the sensor functions in whole urine and serum, and can non-invasively measure DNA and microRNA after implantation in live mice.
NM07.04: Quantum Dot-Based Bioprobes
Session Chairs
Niko Hildebrandt
Fiorenzo Vetrone
Tuesday PM, November 28, 2017
Hynes, Level 3, Room 308
3:30 PM - NM07.04.01
Analysis of Multiplexed Nanosensor Arrays Based on nIR Fluorescent Single Walled Carbon Nanotubes
Juyao Dong 1 , Michael Strano 1
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Show AbstractThe high-throughput, label-free detection of biomolecules remains an important challenge in analytical chemistry with the potential of nanosensor technology to significantly increase the ability to multiplex such assays. Herein, we analyze the variance and binding kinetics of a nanosensor array based on fluorescent single wall carbon nanotubes. The nanotubes are non-covalently modified with Cu2+ chelator - nitrilotriacetic acid group – to immobilize immunobinding proteins, such as Protein A, G and L as molecular recognition sites. The Cu2+ ions also serve as a proximity quencher that when the analyte antibodies bind with the immunobinding proteins, the resulted distance change between the Cu2+ ions and the nanotube surface modulates the near IR emission of nanotubes and gives a direct readout. Based on this mechanism, we develop an optical microarray composed of sensor spots about 200 um at a density of ~300 spots/cm2, which is capable of real-time and quantitative detection of Mouse IgM, Human IgD and Rat IgG2a, in the concentration range between 125 – 500 ug/mL. Moreover, the binding forward reaction rates can be extracted from the initial binding response, which are significantly different among the recognition sites. In order to perform multiplexed detections, the sensor array is modified with Protein G and Protein L in alternative columns, showing distinct binding affinities with the same analyte, demonstrating the capacity to perform high throughput detection with the optical microarray. In addition to the platform development, we also investigate the spot-spot variance, which is shown to result from the inhomogeneous distribution of nanosensors in the spot during the printing and modification process.
3:45 PM - *NM07.04.02
Pursuing New Imaging and Theranostic Applications with Quantum Dots
Igor Medintz 1
1 , U.S. Naval Research Lab, Washington, District of Columbia, United States
Show AbstractThe unique photophysical properties that characterize luminescent semiconductor nanocrystals or quantum dots (QDs) have made them of specific interest for the development of a new generation of optical bioprobes and nanoscale theranostic devices. Relevant properties of interest include size-tunable narrow photoluminescence coupled to broad absorption spectra, some of the highest available multiphoton action cross sections, high quantum yields, strong resistance to photo- and chemical degradation, and the ability to be bioconjugated to display biologicals such as proteins, peptides or even drugs as desired. Moreover, QDs are highly amenable to use as a biosensing signal transduction modality in the context of energy transfer configurations. Some recent efforts and challenges in pursuit of creating new sensors, imaging agents, probes and theranostic devices around QD platforms will be described. These include use of QDs for visualizing neuronal patch clamp probes in brain tissue and live brain. Here, the QD’s unrivaled multiphoton action cross sections allow for easier visualization over longer experimental time periods while using far less laser energy in deep tissue than required with conventional dyes. QD ability to display self-antigenic peptides and generate immunological tolerance in a mouse model of multiple sclerosis will also be highlighted where the density of peptide display correlated with the degree of tolerance. Lastly, the complex issue of QD toxicity will be discussed in the context of a recent meta-analysis study that analyzed data collected from more than 300 publications which cumulatively provided more than 40,000 data points. The latter issue has important ramifications for generalized nanoparticle use in all facets of biological research.
4:15 PM - *NM07.04.03
Indium Phosphide Heterostructures for Biomedical Imaging and Biosensing
Allison Dennis 1
1 , Boston University, Boston, Massachusetts, United States
Show AbstractThe future of semiconductor quantum dots (QDs) in biomedical applications lies not with well-established CdSe-based materials that raise issues of toxicity and limited tissue penetration depths, but rather with heavy metal-free compositions that emit in the near infrared (NIR) and short wave infrared (SWIR) in addition to visible wavelength ranges. We are applying advances in QD synthesis to produce thick-shelled or ‘giant’ QDs (gQDs) comprised solely of InP, ZnSe, and ZnS to generate heavy metal-free visible and NIR emitters for imaging and sensing. While tuning InP core/shell QDs throughout the visible wavelength region is not new, we have adapted gQD chemistry to make brightness-equalized cadmium-free QDs for multiplexed imaging and sensing applications. InP cores of different sizes yield distinct emission peaks, but the emission brightness from the different samples varies significantly because of the vastly different molar extinction coefficients of the small and large InP nanoparticles. We apply shells of ZnSe with variable thicknesses (1-16 atomic monolayers) to the discrete InP cores, balancing the molar absorptivity and the relative brightness of the different emitters. These Type-I semiconductor QDs are being used to simultaneously image the presentation of distinct breast cancer biomarkers in epifluorescence and multiphoton microscopy. When we use the same materials, but rearrange the compositions to make an inverted Type-I semiconductor structure, we are able to push emission wavelengths into the NIR for tissue-depth imaging. These ZnSe/InP/ZnS Inverted Type-I gQDs—dubbed ‘quantum shells’ or QSs because the optical properties are derived from the composition and thickness of the InP shell layer—emit up to 900 nm, i.e., redder than traditional InP cores. These new materials enable the multiplexed imaging of the same breast cancer biomarkers in widefield imaging of whole animals and multiphoton microscopy in tissues. I will discuss the synthesis and characterization of these new materials, their unique photophysical properties, and our application of these QDs,gQDs, and QSs to biomedical imaging and fluorescence resonance energy transfer (FRET)-based sensing.
4:45 PM - NM07.04.04
A Ligand System for Flexible Functionalization of Quantum Dots via Click Chemistry
Yue Chen 1 , Jose Cordero 1 , Moungi Bawendi 1
1 , MIT, Cambridge, Massachusetts, United States
Show AbstractWe present a novel ligand, 5-norbornene-2-nonanoic acid, which has a carboxylic acid group at one terminus of the molecule to bind to the surface of quantum dots (QDs) and a norbornene group at the opposite end that enables straightforward phase transfer of quantum dot into aqueous solutions via efficient norbornene-tetrazine click chemistry. This ligand can be added during established QD syntheses in organic solvents to generate “clickable” QDs at a large scale. The subsequent reaction with 1,2,4,5-tetrazine terminated functionalized polyethylene glycol (PEG) enables water solubilization of QDs with minimal impact on the optical properties. By varying the type and ratio of the terminal groups (azide, maleimide, biotin, etc) of PEG, flexible functionalized QDs were readily obtained. These water soluble QDs maintain 70% of their original quantum yield, small hydrodynamic diameters of about 12 nm, and good colloidal stability. To demonstrate the simplicity and effectiveness of our approach, we show that upon incubation of azido-functionalized CdSe/CdS QDs with 4T1 cancer cells that were pretreated with dibenzocyclooctyne bearing unnatural sugar, QDs exhibit high targeting efficiency and minimal nonspecific binding. Importantly, our ligand system shows excellent versatility to be applied to other carboxylate ligands stabilized nanoparticles such as CdSe/ZnS QDs, CdSe/CdS nanorods, InAs/CdSe/CdS QDs, and PbS QDs.
NM07.05: Poster Session
Session Chairs
Eva Hemmer
Niko Hildebrandt
Jianghong Rao
Fiorenzo Vetrone
Wednesday AM, November 29, 2017
Hynes, Level 1, Hall B
8:00 PM - NM07.05.01
Stacked Gold Nanodisks as Bimodal Plasmonic Bioprobes for Photoacoustic and Optical Coherence Imaging
Jung-Sub Wi 1 , Jisoo Park 1 , Heesung Kang 1 , Sang-Won Lee 1 , Tae Geol Lee 1
1 Center for Nano-Bio Measurement, Korea Research Institute of Standards and Science, Daejeon Korea (the Republic of)
Show AbstractThe light-induced collective oscillation of free electrons in a nanostructured noble metal allows plasmonic nanoparticles to be promising contrast agents for laser-based biological imaging. Accordingly, much effort has been made to synthesize plasmonic nanoparticles having well-controlled geometries which has a strong correlation with the nanoparticles’ light-absorbing and scattering properties as well as the resonant wavelengths. In this study, two-dimensional Au nanodisks and their stacked form, where a smaller sized Au nanodisk was laid atop a larger nanodisk, are reported as advanced nanoprobes for laser-based imaging, because their two-dimensional circular forms are intrinsically conducive to a wide range of resonant wavelengths, tunable ratio of light absorption-to-scattering, and responsiveness to random incident light. Based on our proposed physical synthesis, where gold is vacuum-deposited with a controlled angle onto a prepatterned polymer template and released from the substrate in the form of a nanodisk, we were able to synthesize variously sized monodisperse Au nanodisks and the stacked Au nanodisks (SANs). The measured absorbance of the SANs and the calculated electromagnetic field distributions clearly demonstrated that the SANs combined the optical functionalities of the two different-sized nanodisks as well as their external shapes. The combined optical properties of the SANs—enhanced light absorption at 630 nm and light scattering at 850 nm—were successfully utilized to improve the in vivo image contrast for both photoacoustic microscopy and optical coherence tomography. In light of these results, it is clear that the Au nanodisks and their stacked form can be applied as highly sensitive and multiplexed optical bioprobes.
8:00 PM - NM07.05.02
Cadmium-Free Semiconductor Quantum Shells for Multiplexed Tissue-Depth Imaging
Alexander Saeboe 1 , Margaret Chern 1 , Reyhaneh Toufanian 1 , Joshua Kays 1 , Thuy Nguyen 1 , Allison Dennis 1
1 , Boston University, Boston, Massachusetts, United States
Show AbstractCancer is the second most frequent cause of death in the western world despite concerted research effort. Advanced treatments can be tailored to a specific patient and tumor following determination of specific disease characteristics, typically following biopsy. In situ molecular phenotyping using fluorescence imaging would enable non-invasive determination of tumor characteristics for cancer research as well as in diagnostics and treatment monitoring. We have synthesized multiple near infrared (NIR) emitting cadmium-free quantum dots (QDs)—ZnSe/InP/ZnS core/shell/shell inverse Type-I quantum dots, or ‘semiconductor quantum shells’ (QSs)—targeted to breast cancer cell surface receptors as bright and photostable contrast agents for multiplexed imaging in tissues. These QSs have tunable emission across most of the visible wavelength regime and much of the first near infrared (NIR) tissue imaging window, which extends from 650-950 nm. This tunability extends farther than that of a traditional InP Type-I QD and yields quantum shells with significantly more uniform emission spectra at red wavelengths. By controlling the number of monolayers added to the QSs, we can tune the emission peak from 530 nm to 868 nm (2.34 – 1.43 eV). The full width half maximum (FWHM) of the emission peak remains constant (0.32 eV) as monolayers are added, indicating regular and high-quality shell growth. To confer water solubility, long circulation times, and chemical handles for bioconjugation, the QSs were encapsulated in PEGylated phospholipid micelles functionalized with terminal azido groups. The QSs exhibit good retention of quantum yield and a high degree of monodispersity following encapsulation. Using click chemistry, the terminal azido groups will be conjugated to both an anti-HER2 antibody and an anti-CXCR4 peptide for targeting to cell surface receptors. We have commenced in vivo and in vitro imaging experiments of targeted NIR emitting quantum shells. Due to the relatively narrow FWHM in the NIR, multiplexing of three NIR cadmium-free QSs, has been demonstrated, and can be easily achieved using an IVIS imaging system. The targeted, micelle encapsulated quantum shells have potential as excellent optical contrast agents, given their tunability and brightness. This new class of fluorophores opens the door to multiplexed imaging in murine models, an advancement that we are using to image the evolution of breast cancer markers in longitudinal animal imaging studies.
8:00 PM - NM07.05.03
Gadolinium Nanocrystals with Controlled Size and Surface Chemistry as High-Performance Magnetic Resonance Imaging Contrast Agents
Sha He 1 , Noah Johnson 1 , Viet Anh Nguyen Huu 1 , Adah Almutairi 1
1 , University of California, San Diego, San Diego, California, United States
Show AbstractMagnetic resonance imaging (MRI) has been a widely used clinically diagnostic tool over decades, where the relaxation of water protons in the object is used to extract morphological/anatomical information with high resolution and unlimited tissue penetration. Contrast agents (CAs) shorten the relaxation time of water protons to enhance contrast and gadolinium (Gd3+)-complexes are now one of the most powerful class of CAs applied in both fundamental research and clinical applications. While theoretical model predicts that relaxivity as high as 80-100 mM-1s-1 per Gd3+ at 1.5 T can be achieved, commercial CAs usually have a low relaxivity around 3-5 mM-1s-1. Here we show that using by controlling the size and surface coating of Gd3+-based inorganic nanocrystals, we can push the relaxivity approaching the theoretic limit predicted by the model. Also, with increased relaxivity per Gd3+, it is possible to address the safety concern of injected CAs due to much less applied dosage. Furthermore, the limit of accumulating large local concentration of CAs to observe contrast can also be overcome by our CAs with high relaxivity. Therefore, this type of Gd3+-based high performance MRI CAs is both fundamentally and clinically important.
8:00 PM - NM07.05.04
Giant Enantiomeric Sensitivity of Superchiral Light Fields with Nanofingernails
Roger Chang 2 4 , Paulina Librizzi 2 3 , Aneek Biswas 1 2 , Matthew Moocarme 1 2 , Luat Vuong 1 2 , Ilona Kretzschmar 2 4
2 Graduate Center, The City University of New York, New York, New York, United States, 4 Chemical Engineering, City College of the City University of New York, New York, New York, United States, 3 , Macaulay Honors College, New York, New York, United States, 1 , Queens College of the City University of New York, Flushing, New York, United States
Show AbstractChirality— denoting 3-dimensional structures that are non-superimposable with their mirror image—is extremely common in nature but chiral molecules are challenging to detect with high sensitivity. Scientists have long attempted to optimize chiral light-matter interactions for enantioselective biosensing and molecular separation, towards chiral-asymmetric catalysis and chiral spectroscopic imaging, however, it remains a challenge to detect low concentrations of small chiral analytes. One approach towards the detection of chiral molecules involves manipulating the chirality of the optical fields. Enhanced light chirality or superchiral fields may be produced in sharp electromagnetic-field gradients generally within the near fields of plasmonic nanostructures, where the degree of dissymmetry heightens the interactions between the field and the molecule.
We have combined this new trend of using superchiral optical fields together with bi-metallic effects for further enhancement in the degree of asymmetry in enantiomeric excitations with large-area bottom-up self-assembled nanofingernails. Our fingernail-like 3D chiral metamaterial avoids the pitfalls of costly, difficult, multi-step, unreliable fabrication methods and involves simple sequential thermal evaporation of metals into track-etched substrates. The fabrication technique allows tuning of the resonant frequency by allowing easy modification of the height, thickness and materials of the fingernail-shaped nanostructure. Circular dichroism measurements indicate the CD of individual structures achieve a response of 50% close to the plasmon resonance, in agreement with simulations. We numerically calculate an optical chiral enhancement factor (OCE) greater than 8 near each nanofingernail, which is comparable to previously reported OCE generated in optical microcavities and surpasses numerous top-down-fabricated geometries currently under scrutiny for chiral biosensing. Moreover, high delocalization— where an OCE of 3 is achieved at a distance of 800 nm from the metal surface— is extremely desirable for avoiding fluorescence quenching and indicates that the nanofingernails may be an exceptional substrate for large-area diagnostic test strips.
8:00 PM - NM07.05.05
Rationally Designed Platform for Simultaneous Cancer Detection and Photothermal Therapy—pH Responsive Polymer Decorated MoS2 Sheets
Chan Ho Park 1 , Sang Min Lee 1 , Shin-Hyun Kim 1 , Bumjoon Kim 1
1 , Korea Advanced Institute of Science and Technology, Cambridge, Massachusetts, United States
Show AbstractAcidic extracellular pH is a general feature of cancer tissue and it is of great importance to detect subtle change in pH close to neutral condition (pH 6-8). In this paper, we demonstrate pH-sensing and PT treatment using fluorescent pH-responsive polymer grafted MoS2 (F-MoS2) and show its fluorescence dynamics as a function of pH in the narrow range from 6.0 to 7.4. As a responsive polymer, poly[(2-(diethylamino)ethyl methacrylate)-r-(butyl methacrylate)] labeled by Rhodamine B dyes was precisely controlled the pKa of the polymer using random copolymerization. The pH-dependent optical properties of the F-MoS2 were achieved by exploiting the pH-responsive conformation of the copolymer chains on MoS2 to tune the Förster resonance energy transfer between the red emitters suspended on the polymer and the MoS2 acceptor. Utilizing the strong near-infrared (NIR) absorbance attributed to F-MoS2 included capsules, PT therapy was then conducted with in vitro system to highlight their potential as an in-situ cancer detection and PT therapy agent. Finally, the cancer cells were eliminated over 80 % when the NIR laser exposed for 20 min. Our results suggest that F-MoS2 system is a powerful agent for PT therapy of cancer.
8:00 PM - NM07.05.06
Upconverting Luminescent Nanomaterials—A Liquid-Phase Laser Ablation Approach
Rosemary Calabro 1 , Dong-Sheng Yang 1 , Doo Young Kim 1
1 , University of Kentucky, Lexington, Kentucky, United States
Show AbstractPhoton upconversion is a photophysical process where a material absorbs multiple, low energy photons, often near infrared (NIR), and emits a single higher energy photon, usually in the visible or ultraviolet region. Upconverting nanomaterials have emerged as promising materials for bioimaging and sensing, targeted drug delivery, photodynamic therapy, solar, and security applications due to their ability to convert lower energy light such as near infrared (NIR) to higher energy, visible or UV. NaYF4 codoped with optically active trivalent lanthanides is commonly used for upconverting applications. In this materiel, a Yb3+ sensitizer is excited with 980 nm photons and the photoexcited energy is transferred to an activator ion (such as Er3+, Tm3+, Ho3+, Dy3+, Nd3+) which emits in the visible or ultraviolet. Although traditional methods such as thermal decomposition, solvothermal synthesis, and coprecipitation have been used to produce upconverting nanomaterials with high upconversion quantum yields, these methods have several limitations such as toxic side products, high reaction temperatures, long reaction times and poor control over the phase and morphology. Liquid-phase laser ablation is a promising alternative for nanomaterial synthesis due to its fast production, use of fewer chemicals, production of fewer byproducts, and control over the product through tuning of the laser parameters. In a typical experiment, a NaYF4:Yb3+/Er3+ target is produced through coprecipitation followed by 532 nm pulsed nanosecond laser irradiation in water. The laser causes the formation of plasma plumes which expand, cool, and condense in the water to form particles. The resultant particles show stronger emission at 652 and 669 nm and weaker bands at 407, 488, 523, 544, 556 nm, which can be assigned to various transitions between atomic states of the Er3+ ion. Laser ablation improves upconversion efficiency when compared to the precursor target material. The size of the resultant particles can be controlled by the power of laser used as well as by the presence of capping agents in the liquid during laser ablation. Other laser parameters such as repetition rate, wavelength, and laser ablation duration can be manipulated to control the resultant nanoparticles. These nanoparticles can be coupled to graphene quantum dots for photodynamic therapy applications.
8:00 PM - NM07.05.07
Quantitative and Real-Time Protein Sensors in Single Living Cell Using Aptamer Labeled Single Nanowire
Abebe Cherinet 1 , Moon-Jung Yong 1 , Chong Cook Kim 1 , Seung Soo Oh 1 , Jung Ho Je 1
1 , POSTECH, Pohang Korea (the Republic of)
Show AbstractQuantitative measurements the of proteins in single cells is critical for understanding molecular mechanisms of cellular processes such as disease progression, cell differentiation and provide appropriate biomedical discovery and development of novel therapeutics and diagnostics1. In particular, quantitative and real-time probing of protein in single living cells is essential for early diagnosis of human diseases but largely unexplored due to lack of appropriate probing methods. Cell lysis approaches provide only quantitative probing of protein by destroying cells while optical imaging approaches enable qualitative probing of protein by labeling cells, resulting in cell contamination. Herein, we develop biosensing endoscope based on nanowires that can safely penetrate cell membranes with little cell damage. Specifically, a PMMA nanowire is grown directly to a tapered optical fiber for optical guide within a cell and the surface is functionalized with fluorescence labeled aptamer. The aptamer is used as sensing probes of protein by structure switching via binding between the aptamer and the target protein. The nanowire waveguide endoscope enables us to measure real-time target protein concentration in single living cells. We discuss fluorescent intensity as a function of protein concentration. Our approach of the nanowire waveguide endoscope will significantly contribute to understanding various cellular process.
References
[1] Wu M, Singh AK. Single-Cell Protein Analysis. Current Opinion in Biotechnology. 2012;23(1):83-88
[2] Alireza Abbaspourrad, Huidan Zhang, Ye Tao, Naiwen Cui, Haruichi Asahara, Ying Zhou, Dongxian Yue, Stephan A. Koehler, Lloyd W. Ung, John Heyman, Yukun Ren, Roy Ziblat1, Shaorong Chong & David A. Weitz, scientific report5, 12756 (2015)
[3] Xiliang Luo, Innam Lee, Jiyong Huang, Minhee Yun and Xinyan Tracy Cui, Chem. Commun., 2011, 47, 6368–6370
8:00 PM - NM07.05.08
Brightness-Equalized InP/ZnSe/ZnS Quantum Dot Heterostructures for Multiplexed Imaging
Reyhaneh Toufanian 1 , Thuy Nguyen 1 , Joshua Kays 1 , Alexander Saeboe 1 , Katherine Ward 1 , Allison Dennis 1
1 , Boston University, Boston, Massachusetts, United States
Show AbstractThe size dependent optical properties of quantum dots (QDs) have made them suitable for a broad variety of biomedical imaging and biosensing applications, including the multiplexed imaging of cells and tissues. Simultaneous detection of multiple QDs with distinct emission peaks remains a challenge, however, because of the interplay between particle size and emission color. Specifically, larger QDs of a given semiconductor material emit redder; due to their larger size, they also exhibit increased absorption cross sections, resulting in significantly enhanced brightness compared to smaller, bluer emitters. Dramatic differences in brightness, defined as the product of quantum yield (QY) and molar extinction coefficient at the excitation wavelength (ε), make it impossible for multiple colors to be imaged simultaneously without the intensity of the brightest emitters dwarfing that of the dimmer indicators. Furthermore, heavy metal-based QDs are contraindicated for many biomedical applications due to concerns about toxicity. We address both of these drawbacks to traditional CdSe-based QDs with InP/ZnSe/ZnS core/shell/shell heterostuctures. The size of the InP core and thickness of the ZnSe shell are both modulated to generate an array of heavy metal-free semiconductor fluorophores that exhibit similarly high brightnesses across a range of visible emission wavelengths following excitation at 400 nm. ZnSe shells ranging from 1 – 16 atomic monolayers in thickness were added to colloidal InP cores through a modified successive ion layer absorption and reaction (SILAR) approach; ZnS capping shells were added to further passivate the surface, protect the QDs from oxidation, and maintain high QYs in aqueous media. Thick ZnSe shells were added to smaller InP cores to produce green, yellow, and orange emitters that matched the emission intensity of larger InP cores with the thinnest ZnSe shells. The QDs were encapsulated in lipid-PEG micelles labeled with targeting ligands/antibodies for three distinct extracellular breast cancer biomarkers (HER2/neu, Folate Receptor α, and the cytokine receptor CXCR4) and the relative abundance of these biomarkers was imaged in several breast cancer cell lines. Utilization of these brightness-matched QDs vastly improved detection sensitivity and quantitative multiplexed imaging capabilities, enabling simultaneous imaging of multiple targets.
8:00 PM - NM07.05.09
Quantum Dots in an Amphiphilic Polyethyleneimine Derivative Platform for Ratiometric and Reversible Nitric Oxide Sensing
Junhwa Lee 1 , Sungjee Kim 1
1 , POSTECH, Pohang Korea (the Republic of)
Show AbstractNitric oxide (NO) is a diatomic molecule and plays a key role in a variety of biological processes. NO is highly diffusible and extremely labile by oxidation. In order to analyze NO generation and distribution in vivo, a reliable in vivo NO sensing fluorescent probe is still in pursuit. Quantum dots (QDs) have emerged as an alternative to fluorescence proteins or organic dyes in biological applications. QDs have high the extinction coefficient, broad absorption range, high photostability, and resistance against photobleaching that cannot be paralleled by organic fluorophores. Cationic amphiphilic polyethyleneimine derivatives (amPEIs) were synthesized to encapsulate dozens of QDs and NO sensing metal complex. amPEIs successfully wrapped Fe (III) complexes of a tetra-amido macrocyclic ligand and two kinds of QDs (one emits at around 750 nm and the other at around 450 nm). The Fe complex and QD-amPEI composite was around 100 nm in hydrodynamic size. The composite was used for NO sensing probe. It had slightly positive outer surface that suited well for cellular internalization. Fe complexes could react with dissolved NO molecules outside of the composites and showed immediate appearance of strong absorption in visible (500~650 nm) and near-IR (700~1000 nm) ranges. When NO was purged out in solutions, absorption spectrum of Fe complex returned to the initial state. QDs-Fe complex-amPEI based NO probe demonstrated accurate and reversible NO sensing by the ratiometric photoluminescence signals. In NO saturated solution, quenching of 750 nm emitting QD PL was observed because Fe complex could absorb part of QD PL upon the binding NO to metal center. As NO was released from the Fe complex, the 750 nm QD emission was recovered. In contrast, 450 nm emitting QD acted as an internal standard. The Fe complex showed similar absorption profile at 450 nm regardless of the binding or leaving of NO, and the 450 nm QD emission intensity was independent of the NO concentration. Reversibility of the QDs-Fe complex-amPEI composites was tested by switching the environment between the nitrogen and nitric oxide conditions for more than 5 cycles. These results showed our QD-based nitric oxide sensing platform technology can real-time monitor NO in cells and in vivo models.
8:00 PM - NM07.05.10
Highly Sensitive Luminescent Ratiometric Nanothermometers for Deep-Tissue Thermal Sensing
Pascal Gschwend 1 , Fabian Starsich 1 , Sotiris Pratsinis 1
1 , ETH Zurich, Zurich Switzerland
Show AbstractHyperthermia and thermoablation are upcoming therapies for the destruction of diseased tissue. To reduce unwanted thermal effects on surrounding healthy matter, non-invasive temperature measurements with high spatial resolution at the exact treatment location are necessary. These requirements are not met by commonly applied methods such as IR thermal imaging. Here, BiVO4 nanoparticles doped with Nd3+ and La3+ are presented as luminescent nanothermometers operating in the first biological window (650-950nm), where light absorption and scattering by tissue is strongly reduced. The effect of La3+ codoping on the structural and luminescent properties of BiVO4:Nd3+ is investigated and an optimal composition is found. Most importantly, the potential of these luminescent nanoparticles for nanothermometry based on a ratiometric approach is investigated. A relative thermal sensitivity of up to 1.44%/K at 37 °C was determined, which is among the highest found for such systems operating in the near infrared. The excellent sensitivity of the nanomaterial at physiologically relevant temperatures resulted in a temperature uncertainty of only 0.1 K, which is sufficient for accurate temperature control during photothermal therapy. Finally, the merit of the proposed nanothermometer was demonstrated ex vivo with chicken skeletal muscle tissue proving the feasibility of BiVO4:Nd,La for non-invasive thermometry with high spatial resolution.
8:00 PM - NM07.05.11
Hybrid ZnO Nanoparticle and Polymer Composites for Optical and Antibacterial Applications
Linlin Sun 2 1 , Cungu Cao 1 , Yuan Li 1 , Ming Gao 1 , Thomas Webster 2 1
2 Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou China, 1 , Northeastern University, Dorchester, Massachusetts, United States
Show AbstractWith unique optical properties and biocompatibility, zinc oxide (ZnO) materials have been widely applied in photo-catalysts, sensors, solar cells, ultraviolet lasers, cosmetic products and medical applications. In the past decade, scientists have developed various synthesis methods to produce ZnO and hybrid ZnO nanoparticles, such as the solid state reaction, chemical vaper transport, hydrothermal process, and sol-gel process.
Similar as other metal oxide nanoparticles, ZnO nanoparticles have been found to increase bacterial inhibition with a decrease in particle size, which was mainly caused by the enhanced reactive oxygen species (ROS) production. Moreover, the increased concentration and the light excitation could also enhance antibacterial ability of ZnO nanoparticles.
For optical applications, polymers have been manufactured as windows, glasses, and conductive films owing to their great transparency, light weight, and ease of mass production. However, when exposed to UV radiation, the operational life of these polymers as well as their transparency could be reduced via photo-degradation over time. Previous research indicated that UV-absorbing additives could improve the performance and extend the optical applications of polymers.
In this study, ZnO, Au/ZnO, Ag/ZnO, and Se/ZnO nanoparticles were synthesized for optical and anti-infection applications. The size, morphology, and crystalline structure of hybrid ZnO nanoparticles have been carefully examined using transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet-visible spectra (UV) and energy-dispersive X-ray spectroscopy (EDX). For antibacterial study, Staphylococcus aureus (SA), Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) bacteria were seeded and counted with colonies to evaluate hybrid ZnO polymer composites.
Compared to pristine ZnO, hybrid ZnO nanoparticles induced the red shift of UV absorption peak and the rod-shape morphology. For antibacterial study, ZnO indicated moderate inhibition ability, while Ag/ZnO nanoparticles showed an enhanced toxicity towards all tested bacteria. With the infrared light excitation, hybrid ZnO nanoparticles enhanced the temperature of polymer composites, which also increased the bacteria death ratio. In light of the above results it appears that hybrid ZnO nanoparticle and polymer composites may provide a novel material family for optical and antibacterial applications.
[1] A. Dakhlaoui and M. Jendoubi, J. Cryst. Growth 311, 3989 (2009).
[2] F. Chung and Z. Zhu, Sensor Actuat. B:Chem. 199, 314 (2014).
[3] G. Applerot and A. Lipovsky, Adv. Funct. Mater. 19, 842 (2009).
[4] A. Lipovsky and Y. Nitzan, Nanotech. 22, 105101 (2011).
8:00 PM - NM07.05.12
Solubilization and Functionalization of Upconverting Nanoparticles with Janus Dendrimers
Mirna El Khatib 1 , Shane Plunkett 1 , Ikbal Sencan 2 , Joshua Collins 3 , Sava Sakadzic 2 , Sergei Vinogradov 1
1 , University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2 , Massachusetts General Hospital, Boston, Massachusetts, United States, 3 , Intelligent Material Solutions, Princeton, New Jersey, United States
Show AbstractLanthanide-based upconverting nanoparticles (UCNP's) are able to efficiently convert near infrared excitation energy into visible or higher energy near infrared light, thereby presenting an attractive platform for construction of biological imaging agents. However, lack of solubility and difficulty in their surface modifications hamper development of UCNP's into general imaging agents. Previously, we have demonstrated that shape-persistent polyglutamic dendrimers, exhibiting multiple carboxylate groups at their termini, tightly bind to UCNP surfaces, thus stabilizing them in aqueous solutions.1 However, solubility imparted by polycarboxylates can be negatively affected by the presence of divalent metal cations and various macromolecules (proteins, lipids etc), which are abundant in biological systems. In this work, we extend and generalize our approach by using Janus-type dendrimers, in which one half of the dendrimer features carboxylates for binding to UCNP surfaces, while another is highly hydrophilic, but neutral as a result of extensive PEG-ylation. The new dendritic UCNPs proved to have superior stability and biocompatibility and allowed high-resolution imaging of the brain vasculature in mice up to 1 mm deep into the cortex by means of multiphoton microscopy with continuous-wave infrared excitation sources. The synthesis of PEGylated Janus-dendrimers, possessing a pH-sensitive chromophore as a core, as well as the method of dendrimerization of UCNP's have been optimized and scaled up, featuring a new generally applicable methodology for UCNP solubilization.
References
1 Esipova, T. V.; Ye, X.; Collins, J. E.; Sakadzic, S.; Mandeville, E. T.; Murray, C. B.; Vinogradov, S. A. Proc. Natl. Acad. Sci. U.S.A. 2012,109, 20826.
Support of the grants EB018464 and is gratefully acknowledged.
8:00 PM - NM07.05.14
Synthesis of Functionalized Magnetic-Plasmonic Nanoparticles for Bio-Detection Signal Amplification
Jing Li 1 , David Truong 1 , Jessica Luo 1 , Michael Kozma 1 , Shiyao Shan 1 , Zakiya Skeete 1 , Yan Liu 1 , Maria Hepel 2 , Chuan-Jian Zhong 1
1 , State University of New York at Binghamton, Binghamton, New York, United States, 2 Chemistry, State University of New York at Potsdam, Potsdam, New York, United States
Show AbstractThe ability to manipulate the nanostructures for generating the desired functional properties is essential for exploring their technological applications (e.g., highly-sensitive nanomaterials for early stage cancer detection). One of the key challenges is the creation of nanoprobes with both bio-compatibility, bio-intervention and signal-amplification capabilities while achieving effective biomolecular recognition. This report describes the new findings of an investigation of the synthesis of magnetic nanoparticles with plasmonic functions as multifunctional nanoprobes for surface enhanced Raman scattering (SERS). The nanoprobe consists of nickel-iron core and gold shell which were synthesized by successive hydrothermal and seed-mediated aggregative growth methods. Upon bio-conjugation, they can be magnetically focused on a specific spot in a microfluidic channel, enabling an enrichment of “hot spots” for SERS detection of the targeted biomarkers. Results have demonstrated the desired multifunctional properties, showing a great promise of utilization for bio-detection signal amplification detection. The findings have significant implications for the design of advanced nanomaterials for advancing biosensors.
8:00 PM - NM07.05.15
Controllable Non-Covalent Assembly of Two Types of Nanoparticles for the Preparation of Multifunctional Biomedical Probes
Isabel Gessner 1 , Daniel Moog 1 , Thomas Fischer 1 , Sanjay Mathur 1
1 Institute of Inorganic Chemistry, University of Cologne, Cologne Germany
Show AbstractComposite or hybrid nanostructured materials, which combine the specific properties of each constituent are currently gaining increased interest in research, due to their multifunctionality and their corresponding diversity of possible applications.
Here, we present the controlled combination of two types of oppositely charged nanoparticles, which self-assemble through electrostatic attachment. By making use of a highly sensitive electrokinetic sonic amplitude (ESA) probe, small changes in surface potential can be measured in situ during a titration of both nanoparticle dispersions. In this work, a step by step addition of negatively charged ultrasmall silica nanoparticles (7 nm) to a dispersion of positively charged NaGdF4: Er3+, Yb3+ (100 nm) nanoparticles resulted in the formation of a particulate silica shell around the optically active host particles. In this context, the number of physisorbed silica particles could be precisely controlled by the number of titration steps, as demonstrated by transmission electron microscopy (TEM) images. As-prepared nano-structures enable a side-selective surface functionalization which is of great interest for their employment in nanomedicine.
This method thus represents a novel way for the preparation of composite materials, which can be used for a broad variety of applications including bioimaging. For instance, by replacing silica e.g. with other traceable probes such as gold or iron oxide nanoparticles, promising multimodal imaging platforms could be easily created.
8:00 PM - NM07.05.16
Synthesis and Surface Modification of Magnetic Nanoparticle Clusters-Quantum Dots Composites
Gyudong Lee 1 , Sanghwa Jeong 1 , Jaejung Song 2 , Donghoon Kwon 3 , Joonhyuck Park 1 , Sangmin Jeon 3 , Sungjee Kim 1 2
1 Chemistry, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea (the Republic of), 2 Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea (the Republic of), 3 Chemical Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea (the Republic of)
Show AbstractThe diagnosis and therapy of disease require information of multiple targets. In order to identify multiple biomolecule, an effective strategy for separation and multiplexing is important. A bio-barcoding system that incorporates quantum dots (QDs) and magnetic nanoparticles can be useful for such applications. Silica-shell-coated magnetic nanoparticle clusters (SMNCs) were synthesized and the SMNCs were loaded with QDs using amphiphilic polyethyleneimine derivatives (amPEIs). The resultant a few hundred nanometer sized SMNC-QDs-amPEIs were composed of SMNC core surrounded by hundreds of QDs. SMNC-QDs-amPEIs showed excellent photoluminescene(PL) property and can be facilely collected in presence of an external magnetic field. The PL characteristics of SMNC-QDs-amPEIs can be flexibly tuned by controlling relative amount of different color QDs. By combining different colored QDs, a colored barcode library was demonstrated. The surface of SMNC-QDs-amPEIs was decorated by zwitterionic ligands, which made the barcode library colloidally stable at physiological condition and possess minimal non-specific adsorptions. Zwitterion tethered SMNC-QDs-amPEIs showed enhanced colloidal stability in high salt concentration and under broad pH range. The minimal non-specific adsorption was confirmed by non-specific adsorption level assays using bovine serum albumin or polystyrene coated beads. Some of the primary amines in amPEI moieties were used for bioconjugation of SMNC-QDs-amPEIs. As a proof of concept experiment, SMNC-QDs-amPEIs were conjugated with biotins and the tethering was confirmed by streptavidin bead assays. The remaining amines of amPEIs were cross-linked by bifunctional cross-linking agent for enhanced mechanical integrity of SMNC-QDs-amPEIs. Enhanced integrity was demonstrated by decrease in accessibility of quencher molecule to SMNC-QDs-amPEIs. This surface modified bio-barcode with reduced non-specific adsorption and enhanced integrity can be useful as bio-barcoding agent.
8:00 PM - NM07.05.17
WS2 Nanosheet Biosensors for Pathogen Detection
In-Jun Hwang 1 , Sin Lee 1 , Juhee Han 1 , Tae Woog Kang 1 , Su-Ji Jeon 1 , Jin-Kyoung Yang 1 , Jong-Ho Kim 1
1 , Hanyang University, Ansan South Africa
Show AbstractRecently, designing optical nanobiosensors for the sensitive and selective detection of pathogenic bacteria has attracted considerable attention in nanobio technology and nanomedicine. Among various nanomaterials, two-dimensional (2D) layered WS2 has thickness-dependent optical properties such as fluorescence, Raman scattering and absorption. Hence, it is required to develop an effective method for the synthesis of thin-layered WS2 Nanosheets with intense fluorescence and Raman scattering in aqueous solution. Herein, we demonstrated a carbohydrate-assisted exfoliation method for WS2 nanosheets in water and their application for the selective detection of E.Coli based on the fluorescence quenching. In addition, E.Coli was quantitatively detected with single copy detection sensitivity by measuring the stable Raman scattering signal of exfoliated WS2 nanosheets.
8:00 PM - NM07.05.18
Gd - Gd2O3 Multimodal Nanoparticles as Labeling Agents
Pedro Perdigon Lagunes 1 , Octavio Estevez 1 , Cristina Zorrilla Cangas 1 , Raul Herrera Becerra 1
1 , Universidad Nacional Autonoma de Mexico (UNAM), Mexico City, FDM, Mexico
Show AbstractRecently, lanthanide nanoparticles have captured the attention in many fields, such as energy conversion, sustainability, electronics, photonics and biomedicine. The promise of coupling many imaging techniques into a sole labeling agent has awaken high expectations on personalized medicine or <>. Combining different techniques such as MRI/Endoscopy, CT/PET, CT/MRI, Endoscopy/CT might provide a better treatment approach for hidden diseases. In addition, an interesting aspect of using these type of labeling agents is the opportunity to perform surgical procedures in situ; this gives the possibility of detecting and acting at the same time, increasing the survival rate of the patients.
Therefore, we consider that is highly relevant to investigate these interesting rare – earth base nanoparticles. Hence, our investigation is focused in lanthanide oxide base nanoparticles for biomedical applications.
For this study, we synthesized Gd – Gd2O3 nanoparticles at room temperature by reduction method assisted by Tannic acid, these nanoparticles have shown interesting charge transport interactions. Unexpectedly, our nanoparticles also presented updown conversion effect around the region of 600 – 780 nm with emission between 531 – 576 nm, this characteristic is relevant to be studied. Superficial carbon bounding, which creates prohibited intermediate energy levels. In addition, this carbon layer might increase the biocompatibility. Similar vibrational structures detected by Raman spectroscopy in Gd3+ chelates for MRI. Additionally, the chemistry of Eu3+ and Er3+ ions is compatible with Gd – Gd2O3 nanoparticles; hence, mixture is possible in the synthesis some ions of Eu or Er in order to increase the luminescent response. Furthermore, because of the interesting electronic structure of Gd – Gd2O3 nanoparticles, magnetic labeling is also possible.
Thus, the study of lanthanide base nanoparticles for biomedicine is an enormous field, which requires effort from different research groups that are capable to understand and entwine their different capabilities to be applied in personalized medicine.
8:00 PM - NM07.05.19
Ratiometric Hydrogen Peroxide Biosensing Device with Enzyme-Mimetic Luminescent Nanoparticles
Dorian Henning 1 , Georgios Sotiriou 1
1 , Karolinska Inst, Solna Sweden
Show AbstractHydrogen peroxide (H2O2) is an important (bio)molecule in a variety of bioprocesses and is often decomposed in vivo using the enzyme catalase. Growing interest in quantification of H2O2 exists particularly in pharmaceutical and biological applications, since it is not only a potential biomarker for inflammations and infections, but also an intermediate molecule in enzyme-based assays such as the plasmonic ELISA. However, a label-free, sub-µM, and calibration free assay has yet to be developed. In this work, we propose a nanoparticle-based ratiometric optical biosensor to detect µM and sub-µM quantities of H2O2 in physiological relevant solutions. For this goal, we combine luminescent enzyme-mimetic CeO2:Eu3+ nanoparticles with optically stable Y2O3:Tb3+ nanophosphors [1,2] that serve as concentration independent reference value. Both nanoparticles are synthesized simultaneously in the same single step process, allowing for a highly scalable and reproducible production as well as facilitating direct deposition of this material on glass substrates for the single step fabrication of H2O2 biosensing surfaces. It is shown, that the luminescence properties of the CeO2:Eu3+ nanoparticles vary dramatically for different concentrations of H2O2, allowing for sub-µM limit of detections while the Y2O3:Tb3+ phosphors are highly utilizable as reference material. Hence, the presented material can be used for selective, label-, and calibration-free H2O2 sensing as well as be synthesized in a highly scalable fashion.
[1] Sotiriou, G.A., Schneider, M., & Pratsinis, S.E. (2011) J. Phys. Chem. C 115, 1084-1089.
[2] Sotiriou, G.A., Franco, D., Poulikakos, D., & Ferrari, A. (2012) ACS Nano 6, 3888-3897.
8:00 PM - NM07.05.21
Dual-Color Fluorescent Nanoparticle Showing Color-Specific Photoswitching for Bioimaging and Super-Resolution Microscopy
Dojin Kim 1 , Keunsoo Jeong 2 , Hyeonjong Park 2 , Ji Eon Kwon 1 , Sehoon Kim 2 , Soo Young Park 1
1 Department of Materials Science and Engineering, Seoul National University, Seoul Korea (the Republic of), 2 , Korea Institute of Science and Technology, Seoul Korea (the Republic of)
Show AbstractFluorescence photoswitchable nanoparticle, which can turn on/off its fluorescence reversibly by light irradiation, has been attracting great attention because of its potential in fluorescence bioimaging and super-resolution microscopy.1 It could not only be used to selectively image the bio-systems such as cell, organelles and proteins, but also allow the reconstruction of super-resolution image based on various principles like PALM and STORM. However, the current fluorescent photoswitchable probes have critical shortcoming in bioimaging field because it is hard to trace the movement of probes in live cell when they are in “switched-off state”. To overcome this hurdle, several groups including us proposed color-specific photoswitching in dual-color fluorescence system, of which the switching efficiency is yet too low because complicated intermolecular energy transfer pathways between fluorophores and/or photoswitchable chromophores are involved.2-7 Herein, novel strategy of color-specific photoswitchable nanoparticle with dual-color fluorescence is rationally designed based on the turn-on type fluorescent diarylethene and excited-state intramolecular proton transfer (ESIPT) fluorophore. This nanoparticle represents an entirely new photophysical principle of color-specific photoswitching, which combines the frustration of energy transfer due to ESIPT process and the complete off-to-on switching of diarylethene fluorescence. Significantly, this system could achieve 100 % switching of diarylethene emission while keeping ESIPT emission invariant. Based on this innovative concept, we could synthesize water-soluble and bio-compatible nanoparticle containing those two components of which emission could be tuned from orange to white by photoswitching. Finally, in vitro super-resolution imaging of the nanoparticle could be successfully demonstrated.
Reference
1. Z. Tian, W. Wu, and A. D. Q. Li, ChemPhysChem, 2009, 10, 2577.
2. J. Folling, S. Polyakova, V. Belov, A. Blaaderen, M. L. Bossi, and S. W. Hell, Small, 2008, 4, 134.
3. S. A. Diaz, L. Giordano, T. M. Jovin, and E. A. Jares-Erijman, Nano Lett., 2012, 12, 3537.
4. S. Kim, S.-J. Yoon, and S. Y. Park, J. Am. Chem. Soc., 2012, 134, 12091.
5. S. A. Diaz, L. Giordano, J. C. Azcarate, Thomas M. Jovin, and E. A. Jares-Erijman, J. Am. Chem. Soc., 2013, 135, 3208.
6. T. Wu, J.-C. Boyer, M. Barker, D. Wilson, and N. R. Branda, Chem. Mater., 2013, 25, 2495.
7. D. Kim, J. E. Kwon, and S. Y. Park, Adv. Opt. Mater., 2016, 4, 790.
8:00 PM - NM07.05.22
Fluorescence Resonance Energy Transfer (FRET) with Bright, Cadmium-Free, Semiconductor Quantum Shells for Tissue-Depth Sensing
Margaret Chern 1 , Andrew Mahler 1 , Thuy Nguyen 1 , Alexander Saeboe 1 , Reyhaneh Toufanian 1 , Allison Dennis 1
1 , Boston University, Boston, Massachusetts, United States
Show AbstractNear infrared (NIR) fluorescent optical biosensors hold promise for improved in vivo sensing by taking advantage of increased penetration depths in the first optical tissue window. Our NIR-emitting, heavy metal-free, inverted type-I quantum dots – or ‘quantum shells’ (QSs)— exhibit bright NIR emission that is modulated using Förster resonance energy transfer (FRET) for tissue-based biosensing. The QS heterostructure consists of a ZnSe core and InP shell, where the thickness of the InP shell is used to tune emission wavelength. A third material, ZnS, is used to further protect the optical properties of the QD donor after transfer to aqueous media. The ZnSe/InP/ZnS QSs are tunable over a wide emission range (530 nm to 870 nm), with multiple colors in the near infrared (NIR). These InP QSs are used as Förster resonance energy transfer (FRET) donors in a turn-on sensor for matrix metallopreoteinase (MMP) activity. MMPs are secretory endopeptidases that have been associated with cancer-cell invasion and metastasis. Previous studies have developed FRET sensors emitting in the visible spectrum that can reliably monitor MMP activity in living cells in vitro; use of the NIR QSs as the FRET donor extends this sensor to in vivo applications. The sensor design consists of a 730 nm emitting QS attached to a quencher (IRDye® QC-1) or NIR dye (Cy7) via a peptide cleavage sequence for MMP-7. In the first case, the QS emission is quenched while the MMP-7 peptide is intact, while in the second QS emission is quenched and Cy7 emission is detectable. The two sensor designs result in a one-color turn-on sensor or a ratiometric two-color sensor, respectively. In the presence of MMP-7, the peptide is cleaved, causing the quencher or dye to drift away from its QS donor. In the absence of energy transfer, the visibility of the QS increases dramatically. These two sensors are thoroughly characterized in vitro and their performance in multiphoton microscopy is demonstrated.
8:00 PM - NM07.05.23
Synthesis of Fluorescent Polymer Nanoparticles for Dual Sensing of Biomolecules
Taek Seung Lee 1 , Daigeun Kim 2
1 , Chungnam National University, Daejeon Korea (the Republic of), 2 , Korea Photonics Technology Institute, Gwangju Korea (the Republic of)
Show AbstractPeculiar properties of conjugated polymers, such as conducting properties, thermal stability, and emission properties, enable them to use in organic light-emitting diodes, organic thin film transistors, organic photovoltaic cells, chemical sensors, and biosensors. A great deal of interest has been focused on nano-sized materials including fibrous materials, particulates, and tubes to pursue versatile applications of optoelectronic devices, multimodal imaging, and biomedical medicine. We developed a hybridization technique of fluorescent conjugated polymer nanoparticles (CPNs) with smaller magnetic nanoparticles (MNPs). The MNPs-induced fluorescence quenching of CPNs was observed upon hybridization because the aggregation between two kinds of nanoparticles took place. Such fluorescence quenching was eliminated to recover initial fluorescence of CPNs in the presence of suitable enzyme, which could hydrolyze a linker polypeptide between CPNs and MNPs, leading to deaggregation of both nanoparticles. Thus changes in the dual signals, including fluorescence and magnetism, could be used as sensing signals of the enzyme. As a versatility of this system, any enzyme could be detected by use of appropriate polypeptide which could be degraded by the enzyme to be detected.
8:00 PM - NM07.05.24
Interaction Investigation between Human Serum Albumin and AgInZnS-Graphene Oxide Quantum Dots
Xiaogang Lin 1 , Lingdong Weng 1 , Wei Hu 1 , Xiaosheng Tang 1 , Nan Wan 1
1 , Key Laboratory of Optoelectronic Technology and Systems of Ministry of Education of China, Chongqing University, Chongqing China
Show AbstractGraphene oxide (GO) modified AgInZnS quantum dots (AIZS-GO QDs) have attracted much attention in biological and biomedical fields. The interaction between AIZS-GO QDs and human serum albumin (HSA) has significant meaning in vivo biological application. Herein, the binding of AIZS-GO QDs and HSA was systematically investigated by fluorescence spectra, UV-Vis absorption spectra, FT-IR spectra and circular dichroism (CD) spectra under the physiological conditions. The fluorescence spectra results indicated that AIZS-GO QDs could induce intrinsic fluorescence of HSA quenching effectively. The quenching mechanism was static quenching, which means that some kinds of complex were produced by the binding of QDs and HSA. This result was further proved by UV-Vis absorption spectroscopy. The banding constants at different temperatures (298 K, 303 K, 308 K) were obtained from Stern-Volmer analysis of the fluorescence quenching data. The thermodynamic parameters calculated by Van’t Hoff equation clearly indicated that the van der Waals and hydrogen bonds played major role in the interaction. As further revealed by FT-IR spectroscopy and circular technique, AIZS-GO QDs could change the secondary structure of HSA.
Symposium Organizers
Eva Hemmer, University of Ottawa
Niko Hildebrandt, Université de Paris Sud
Jianghong Rao, Stanford University School of Medicine
Fiorenzo Vetrone, University of Quebec-Instutitut National de la Recherche Scientifique
Symposium Support
ACS Nano | ACS Publications
ACS Photonics | ACS Publications
MilliporeSigma (Sigma-Aldrich Materials Science)
Photon etc
NM07.06: Lanthanide-Based Bioprobes—Synthesis, Characterization and Surface Modification
Session Chairs
Wednesday AM, November 29, 2017
Hynes, Level 3, Room 308
8:45 AM - NM07.06.01
Optically Stable and Near-UV Activated Nanophosphors for Bioimaging and In Vitro Dosimetry
Anastasia Spyrogianni 2 , Peter Tiefenboeck 2 , Jean-Christophe Leroux 2 , Sotiris Pratsinis 2 , Georgios Sotiriou 1
2 , ETH Zürich, Zurich Switzerland, 1 , Karolinska Inst, Solna Sweden
Show AbstractLuminescent rare-earth-based inorganic nanoparticles (nanophosphors) are promising bioimaging agents due to their high photostability, sharp emission bands and high biocompatibility overcoming toxicity-related concerns associated with the commonly-used heavy-metal containing quantum dots. Flame aerosol technology provides a scalable and highly reproducible process for production of such nanophosphors (e.g. Y2O3:Eu3+,Tb3+) with precise control of their composition and properties [1,2,3]. Nanophosphors that can be excited in the near-ultraviolet and visible region, such as YVO4:Eu3+,Bi3+, provide a useful tool for bioimaging and in vitro dosimetry studies using conventional fluorescence microscopes.
Here, YVO4:Eu3+,Bi3+ nanophosphors are made by flame spray pyrolysis. The optimal Bi content for maximum red-shift of their excitation band edge towards the visible region is identified through systematic experiments. The nanophosphors with the optimal composition are highly crystalline and appear bright red under a conventional fluorescence microscope. Their photostability during dynamic imaging of HeLa cells in vitro is confirmed, contrary to commercial fluorescent (organic-dye labeled) SiO2 nanoparticles that exhibit 50% photobleaching within 3.5 h. Furthermore, the deposition rate of these nanophosphors is measured by optical absorption spectroscopy, indicating slower deposition rate in serum-containing than serum-free cell culture medium, consistent with previous studies for different nanomaterials [4]. This is also confirmed in vitro by monitoring the fluorescence intensity of images of HeLa cells after incubation with nanophosphor suspensions in the presence and absence of serum for various time points.
[1] Sotiriou, G.A., Schneider, M., & Pratsinis, S.E., J. Phys. Chem. C 115, 1084-1089 (2011) .
[2] Sotiriou, G.A., Schneider, M., & Pratsinis, S.E., J. Phys. Chem. C 116, 4493-4499 (2012).
[3] Sotiriou, G.A., Franco, D., Poulikakos, D., & Ferrari, A., ACS Nano 6, 3888-3897 (2012).
[4] Spyrogianni, A., Herrmann, I.K., Lucas, M.S., Leroux, J.C., & Sotiriou, G.A., Nanomedicine 11, 2483-2496 (2016).
9:00 AM - *NM07.06.03
Absolute Fluorescence Measurements > 800 nm—Setup Design, Challenges and Characterization of Semiconductor and Lanthanide-Based Nanocrystals
Ute Resch-Genger 1 , Christian Wuerth 1 , Marco Kraft 1 , Martin Kaiser 1
1 , Federal Institute for Materials Research and Testing, Berlin Germany
Show AbstractThere is an increasing interest in optical reporters like semiconductor and lanthanide-based nanocrystals with emission > 800 nm and recently also > 1000 nm for bioanalysis, medical diagnostics, and safety barcodes [1]. Mandatory for the comparison of different emitter classes and the rational design of the next generation of reporters for the short wavelength infrared (SWIR) region are reliable and quantitative photoluminescence measurements in this challenging wavelength region. This is of special relevance for nanocrystalline emitters like semiconductor quantum dots and rods as well as for upconversion and downconversion nanocrystals, where surface states and the accessibility of emissive states by quenchers largely control accomplishable quantum yields and hence, signal sizes and detection sensitivities from the reporter side. Such measurements are currently hampered by the lack of suitable methods and standards for instrument calibration and validation as well as by the lack of quantum yield standards with emission > 800 nm and especially > 1000 nm [2-4].
In this respect, we present the design of integrating sphere setups for absolute and excitation power density-dependent measurements of emission spectra and quantum yields in the wavelength region of 650 to 1650 nm including calibration strategies and first candidates for potential fluorescence standards [3-5]. Subsequently, the photoluminescence properties of different types of nanocrystals are presented and discussed including absolute photoluminescence measurements of upconversion and down conversion emission in different solvents.
Key words: NIR, IR fluorescence, quantum dot, upconversion nanocrystal, lanthanide emitter, integrating sphere spectroscopy, absolute fluorescence quantum yield
References. [1] Hemmer E.; Benayas A.; Legare F., Vetrone F., Nanoscale Horizons 2016; 1, 168-84. [2] Semonin, O. E.; Johnson, J. C.; Luther, J. M.; Midgett, A. G.; Nozik, A. J.; Beard, M. C., J. Phys. Chem. Lett. 2010, 1, 2445-2450. [3] Hatami, S.; Wurth, C.; Kaiser, M.; Leubner, S.; Gabriel, S.; Bahrig, L.; Lesnyak, V.; Pauli, J.; Gaponik, N.; Eychmuller, A.; Resch-Genger, U., Nanoscale 2015, 7, 133-143. [4] Kaiser, M.; Würth, C.; Kraft, M.; Hyppänen, I.; Soukka, T; Resch-Genger, U., Nanoscale 2017, under revision. [5] Würth C.; Kaiser, M.; Wilhelm, S.; Grauel B.; Hirsch T.; Resch-Genger U., Nanoscale 2017, 9, 4283-94.
9:30 AM - NM07.06.04
Multilayer Core-Shell Lanthanide Nanoparticles for Biomedical Diagnostic and Therapeutic Applications
Sha He 1 , Noah Johnson 1 , Viet Anh Nguyen Huu 1 , Adah Almutairi 1 , Jesse Jokerst 1
1 , University of California, San Diego, San Diego, California, United States
Show AbstractDue to the versatile optical/magnetic properties of lanthanide elements, nanoparticles doped with multiple lanthanide ions have been attracting research interest in fabricating multifunctional bio-probes integrated different diagnostic/therapeutic capabilities. However, challenges are there in properly designing and synthesizing multilayer, epitaxially-grown nanoparticles with desired size, shape and layered structures. Herein we have systematically investigated the ionic properties of lanthanides and developed strategies in preparing uniform and monodispersed multilayer lanthanide core-shell nanoparticles. These nanoparticles are concentric, with distinct layers composed of different lanthanide elements. Each element is responsible for different function and they are not interfering with each other. For example, these nanoparticles have significant enhancement in both upconverting and downconverting photoluminescence, making them good candidate for optical imaging probes and photodynamic therapy transducers. Also, these nanoparticles have enhanced relaxivity for MRI because of large particle size compared to conventional small molecule chelate contrast agents. Overall, the versatility of our system makes it highly promising for fabricating multifunctional bio-probes suitable for simultaneous imaging and therapy.
10:15 AM - NM07.06.05
Nanophosphors with Tunable Luminescence Designed via Adaptive Absorption of Transition Metal Ions
Pragathi Darapaneni 3 , Alexander Meyer 2 , Raju Kumal 2 , Mohammad Saghayezhian 5 , Kenneth Lopata 2 , Louis Haber 2 , Ward Plummer 5 , Orhan Kizilkaya 4 , Yuanbing Mao 1 , James Dorman 3
3 Chemical Engineering, Louisiana State University, Baton Rouge, Louisiana, United States, 2 Chemistry, Louisiana State University, Baton Rouge, Louisiana, United States, 5 Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana, United States, 4 , Center for Advanced Microstructures and Devices, Baton Rouge, Louisiana, United States, 1 Chemistry, University of Texas Rio Grande Valley, Edinburg, Texas, United States
Show AbstractOver the past few decades, the development of light emitting diodes (LEDs) to produce wide range of wavelengths has revolutionized the solid state lighting industry because of their higher energy efficiency and lifetime. These LEDs employ rare earth (RE) doped phosphors owing to the stable emission wavelengths which can be amplified when sensitized with other RE elements (Yb, Ce) or shell layer passivation. However, there has been a push to replace the RE elements in LEDs due to increased economic and national security issues. One proposed alternative, transition metal (TM) dopants, is typically avoided due to their crystal lattice dependent optical properties. Despite their susceptible nature, there is motivation to use TM sensitizers in order to design tunable luminescent phosphors through the coupling of RE-TM ions for enhanced energy transfer. The current project demonstrates the ability to tune the optical properties of upconversion phosphors, allowing for controlled absorption and emission spectra.
In this work, β-NaYF4:Er core nanoparticles were synthesized by different wet chemistry techniques such as hydrothermal, thermal decomposition etc. for sizes between 20-500 nm, with TiO2:Ni2+ shell layers deposited via sol-gel chemistry. Initial optoelectronic characterization was performed on ~50 nm thin films of TiO2:Ni, formed by spin coating the gel used for shell layer. Strong localized external fields were generated by surface functionalization of the thin films with various benzoic acid ligands to modify the dipole up to 9 D. X-ray absorption and X-ray photoelectron spectroscopy studies; showed the ability to control the Ni core and valence energy levels by ~0.1 eV shift, without changing the oxidation states of cations or local crystal structures. These shifts were further confirmed via ultraviolet photoelectron measurements and suggest the ability to selectively modify d-orbital hybridization. In order to confirm this phenomenon, time-dependent density functional theory (TD-DFT) simulations were performed on TiO2:Ni bulk-mimicking clusters, and the results were compared to the ligand field theory. The upconversion emissions of the β-NaYF4:Er|TiO2:Ni core-shell nanoparticles was investigated through ultrafast laser studies, showing absorption shifts up to 100 nm and dynamic emission kinetics for each functionalization. Finally, the luminescent intensity of Er3+ upconversion emissions was also systematically controlled with the dipole strength of the ligand. These proof of concept materials demonstrate the ability to control luminescence of solid state phosphors which have the potential to influence lighting, solar conversion, and biological detection.
10:30 AM - NM07.06.06
The Design of Polymer-Coated Upconversion Nanoparticles for Biomedical Applications—Surface-Initiated Light-Regulated Polymerization
Ali Bagheri 1 , Cyrille Boyer 2 , May Lim 1
1 School of Chemical Engineering, University of New South Wales, Sydney, New South Wales, Australia, 2 Centre for Advanced Macromolecular Design (CAMD) and Australian Centre for NanoMedicine (ACN), School of Chemical Engineering, University of New South Wales, Sydney, New South Wales, Australia
Show AbstractUpconversion nanoparticles (UCNPs) have become one of the most active research areas within the nanoscience community due to their unique photoluminescent properties. These nanoparticles can adsorb low energy near infrared (NIR) photons and emit high-energy radiation in the ultraviolet (UV), visible and shorter wavelengths of NIR. This unique property enables a wide range of biomedical applications. These applications often involve the surface modification of UCNPs with other functional materials to create a single platform to enhance and broaden their use.1,2 One such system that is receiving a lot of interest is a hybrid of UCNPs and polymers to render these nanoplatforms water-dispersible and biocompatible. Usually, embedding of UNCPs in hydrophilic polymer nanoparticles carried out using ligand exchange process. However, most of the developed systems in recent years, could not meet the demand to modify UCNPs with molecular diversity and controllability due to the constraint of attaching pre-formed polymers to the particles.3 Therefore, a facile and general strategy is greatly demanded to offer controllability over designing desired nanoplatforms. In this work, for the first time, a surface-initiated photoinduced electron/energy transfer reversible addition–fragmentation chain transfer (PET-RAFT) polymerization (“grafting from”) technique was employed to grow polymer brushes from the surface of UCNPs. Using this approach not only facilitates molecular diversity and controllability to decorate UCNPs, but also offers high degree of control over grafting density and thickness of polymer brushes. Interestingly, the thickness of polymer chains could also be fine-tuned by external temporal regulation on the “ON/OFF” pattern using light. By limiting the non-radiative decay caused by surface defects, as well as from vibrational deactivation from solvents, the polymer shell enhanced the upconversion luminescence of the UCNPs by approximately 20%. This investigation will pave the way for the development of new generations of UCNPs which can be decorated with diverse polymers with externally tuneable thicknesses to meet various application requirements.
1 A. Bagheri, H. Arandiyan, C. Boyer and M. Lim, Adv. Sci., 2016, 3, 1500437.
2 A. Bagheri, J. Yeow, H. Arandiyan, J. Xu, C. Boyer and M. Lim, Macromol. Rapid Commun., 2016, 37, 905–910.
3 A. Sedlmeier and H. H. Gorris, Chem. Soc. Rev., 2015, 44, 1526–1560.
4 A. Bagheri, H. Arandiyan, N. N. M. Adnan, C. Boyer and M. Lim, Macromolecules, 2017, acs.macromol.7b01405.
10:45 AM - NM07.06.07
Glutathione Modified Ultra-Small NIR Emission Rare-Earth Down-Conversion Nanoparticles Covalent Cross-Linking for In Vivo Bioimaging and Renal Clearance
Mengyao Zhao 1
1 , Fudan University, Shanghai China
Show AbstractNanoparticles with hydrodynamic diameter ＜ 5.5 nm have renal clearance metabolism but remain the enhanced permeability and retention (EPR) effect. However, their low enrichment capacity at tumor area hampers the effectiveness of in vivo bioimaging. Here in, we introduce glutathione modified ultra-small NIR emission rare-earth down-conversion nanoparticles (DCNPs) with a hydrodynamic diameter ~ 5 nm to covalent cross-linking responding to the reactive oxygen species (ROS) in tumor microenvironment, thus can prolong the retention time and increase the tumor enrichment of DCNPs. At the same time, the ultra-small DCNPs can be rapid excreted from the body by renal clearance. Our strategy may provide a new method to improve the efficiency of ultra-small nanoparticles bioimaging while keeping the rapid metabolism by renal clearance.
NM07.07: Lanthanide-Based Bioprobes—Immunoassays
Session Chairs
Wednesday PM, November 29, 2017
Hynes, Level 3, Room 308
11:00 AM - *NM07.07.01
Photon-Upconversion Nanoparticles Give a New Twist to Classic Analytical Tools
Hans Gorris 1 , Matthias Mickert 1 , Zdeněk Farka 2 1 , Antonín Hlaváček 3 2 1
1 , University of Regensburg, Regensburg Germany, 2 CEITEC, Masaryk University, Brno Czechia, 3 Institute of Analytical Chemistry, Czech Academy of Sciences, Brno Czechia
Show AbstractConventional fluorescence spectroscopy is limited by autofluorescence and light scattering of the surrounding matrix. This optical background interference can be elegantly avoided by using photon-upconversion nanoparticles (UCNPs) that emit short-wavelength light under near-infrared (NIR, 980 nm) excitation (anti-Stokes emission) [1]. I will describe new nano-analytical techniques taking full advantage of UCNPs. Agarose gel electrophoresis enables the separation and purification of UCNPs [2] that can then be detected in the gel by a 980-nm laser scanner [3]. The purifiation of UCNPs bioconjugates has the potential to improve many bioanalytical applications [4]. Such well-defined UCNPs can be used to replace conventional enzyme-mediated amplification systems in microtiter plate immunoassays. For example, an upconversion-linked immunoassay (ULISA) allowed for the sensitive detection of the pharmaceutical diclofenac in environmental water samples [5]. UCNPs can be detected at the single nanoparticle level using a relatively simple wide-field upconversion microscope. In this way, it is possible to implement a single molecule sandwich immunoassay for the detection of diagnostic markers such as prostate-specific antigen (PSA).
References:
[1] M. Haase, H. Schäfer (2011). Angew. Chem. Int. Ed. 50, 5808.
[2] A. Hlaváček, A. Sedlmeier, P. Skládal, H.H. Gorris. ACS Appl. Mater. Interfaces 6 (2014) 6930.
[3] A. Sedlmeier, A. Hlaváček, L. Birner, M.J. Matthias; V. Muhr, T. Hirsch, P.L.A.M. Corstjens, H.J. Tanke, T. Soukka, H.H. Gorris. Anal. Chem. 88 (2016) 1835.
[4] A. Sedlmeier, H.H. Gorris (2015): Chem. Soc. Rev. 44, 1526.
[5] A. Hlaváček, Z. Farka, M. Hübner, V. Hornáková, D. Němeček, R. Niessner, P Skládal, D. Knopp, H.H. Gorris. Anal. Chem. 88, 6011.
11:30 AM - *NM07.07.02
Upconverting Nanophosphor Reporters for Ultrasensitive Immunoassays
Satu Lahtinen 1 , Annika Lyytikäinen 1 , Nina Sirkka 1 , Henna Päkkilä 1 , Tero Soukka 1
1 , University of Turku, Turku Finland
Show AbstractImmunoassays are widely employed in in vitro diagnostics to measure tiny concentrations of substances of interest from complex biological samples. These assays generally rely on the structural specificity of antibody-antigen binding interaction and the high specific activity of the reporter system to achieve low detection limits. Upconverting nanophosphors (UCNPs) are an attractive choice as a photoluminescent reporter due to their unique capability to convert near-infrared excitation to visible light. Upconversion luminescence (UCL) detection enables total elimination of autofluorescence and potentially unprecedented sensitivity. The analytical sensitivity in solid-phase immunoassays is ultimately only limited by the separation and the non-specific binding interactions of the reporter conjugate.
Cardiac troponin (cTn) I is a clinically significant biomarker, which is used in diagnosis of acute myocardial infarction. It is an example of a biomarker that requires an ultra-low limit of detection to enable improved early diagnosis and to identify patients at risk for cardiovascular diseases. Thus, cTnI was chosen as a model analyte for an ultrasensitive immunoassay using NaYF4:Yb3+,Er3+ UCNPs as reporters. Oleic acid surface ligands on UCNPs (ca. 30 nm in diameter) were removed with acid treatment and the nanophosphors were coated with poly(acrylic acid) (PAA; Mw 2000). An anti-cTnI monoclonal antibody (Mab-1) was conjugated covalently to PAA-coated UCNPs with carbodiimide chemistry. In the immunoassay, biotinylated anti-cTnI antibody Mab-2 and Fab-3 fragment were first immobilized to streptavidin-coated microtiter wells, and cTnI calibrators and cTnI added plasma samples were incubated in the wells for 30 min and the wells were washed. Thereafter, the Mab-1-conjugated UCNPs were incubated for 15 min in a buffer comprising unconjugated PAA, and the wells were washed four times. cTnI was detected from dry wells by measuring the UCL at 525-550 nm with a dedicated upconversion microplate reader equipped with 980 nm diode laser.
The developed antibody-UCNP conjugate based immunoassay allowed highly sensitive detection of cTnI from buffer and plasma. The obtained limit of detection (blank plus three times standard deviation) was down to 0.5 ng/l and the calibration curve was linear up to cTnI concentration 50000 ng/l. The addition of unconjugated PAA to the incubation buffer of Mab-1-conjugated UCNPs resulted in decreased background with blank and increased response with cTnI calibrators. This was concluded to be an effect of PAA masking the non-specific interactions of antibody-UCNP conjugates with the protein coated microtiter well surface. Since the measured assay background with blank was still over ten times higher than the background obtained by excluding the antibody-UCNP conjugate, there is still potential for further improved limit of detection through additional reduction of non-specific binding interactions.
NM07.08: Plasmonic Bioprobes
Session Chairs
Alexander Govorov
Fiorenzo Vetrone
Wednesday PM, November 29, 2017
Hynes, Level 3, Room 308
1:30 PM - NM07.08.01
Development of Ultra-Thin Nanoporous Metal-Insulator-Metal SERS Substrates for Recognizing Tumor Cells
Sevde Altuntas 1 , Fatih Buyukserin 1
1 Biomedical Engineering Department, TOBB University of Economics and Technology, Ankara Turkey
Show AbstractSurface enhanced Raman Spectroscopy (SERS) is a versatile strategy to improve biosensor platforms, which can be combined with aptamers, antibodies or other recognition elements. The spectroscopic technique can potentially allow single molecule detection in solutions or solid surface and it does not need to high expertize and cost. In addition, SERS signal from a target molecule can be further increased by using metallic nanotopographic structures when compared to smooth counterparts. Moreover, these molecule specific Raman signals supply comment about content of samples. However, control of signal reproducibility and intensity are the currently significant issues for the SERS substrates which have many potential problems such as lack of periodicity of surfaces, small scale fabrication and high cost. Nowadays, in order to obtain periodic structures lithographic techniques are commonly used, but aforementioned problems should be solved. In addition to this, it was reported that metal evaporated lithographic structure did not provide high signal efficiency because of weak tunability of plasmonic resonance.1 To resolve this issue metal-insulator-metal (MIM) systems is proposed, but MIM system should be combined with non-lithographic techniques to obtain more effective substrates.
Anodic aluminum oxide (AAO) film is one of the good candidates to fabricate ultra-thin MIM structure with non-lithographic techniques. AAO has tunable periodic nanopores and thickness and it can behave like an optical waveguide.2 Our study proposes to fabricate Au-ultra thin AAO-Ag MIM devices to enhance SERS signals via hot spot occurrence on nanotopographic surfaces. In this context, AAO was fabricated by using voltage reduction method in 0.3 M oxalic acid solution at 7 °C on pure Al foils. To seal AAO film from Al foil, the substrate was immersed in v/v 10% H3PO4 solution at room temperature. Al free AAO film was then spin-coated with 300 µl wt./v 6% polycarbonate (PC) solution to protect one side of the AAO film. Non-protective side of the film was contacted in a dilute acid solution for different time to understand effect of film thickness on SERS spectra which were collected by using methylene blue. Immersion for 8 minutes was reduced to AAO film thickness up to 400 nm. In addition, Au thickness was controlled and SERS spectra were collected from 10 random points for 3 different gold thickness (n=3). Our results showed that 20 nm Au gold coated ultra-thin MIM (500 nm, 10 cm2 area) devices have much more enhanced signal compared to flat counterpart at 1620 cm-1. Enhancement factor and limit of detection studies were completed under same SERS conditions. In the future, anti-Her 2 receptors which are breast carcinoma markers will be decorated on these MIM substrates and cellular recognition study will be conducted.
1. Xu K. et al. 2017 Opto-Electronic Engineering, 44,2
2. Lazzara T. et al. 2010 Journal of Nanoscience and Nanotechnology, 10,7
1:45 PM - *NM07.08.02
Synthesis of Janus Magneto-Plasmonic Nanoparticles—Multimodal Imaging and SERS Detection
Javier Reguera 1 2 3 , Dorleta Jiménez de Aberasturi 1 3 , Malou Henriksen 1 3 , Judith Langer 1 3 , Luis Liz-Marzan 1 2 3
1 , CIC biomaGUNE, San Sebastián Spain, 2 , Ikerbasque, Bilbao Spain, 3 , Ciber BBN, San Sebastián Spain
Show AbstractMulticomponent nanoparticles have attracted strong interest in the last years due to the unique combination of properties present at the nanoscale that make them suitable for a high set of applications. Among them, Janus nanoparticles (with two chemically different surface regions) have emerged as exceptional candidates toward many technological and biomedical applications. Their strong interaction with interfaces has been used e.g. to create emulsified nanoreactors, filtering nanomembranes, or block-copolymers with optical and electronic properties. Other uses include: antireflecting surfaces, electronic displays, nanoswimmers, or as building blocks for more complex molecular colloids and supracrystals. They offer extraordinary potential in biomedicine, as they can mimic natural biomolecules, have directed interactions with cell membranes, or offer regions with high concentrations of biofunctional molecules, while keeping multiple functionalities.
Here, we report the synthesis of Janus nanoparticles composed of Au-Fe3O4 nanostar-nanosphere through two consecutive seed-mediated-growth steps [1, 2]. The nanoparticles showed superparamagnetic properties and a high plasmonic absorption at the near-IR. The extraordinary versatility of these nanoparticles has been tested in analytical sensing using Surface-enhanced Raman spectroscopy (SERS), and multimodal imaging. The resulting experiments showed the high Raman enhancement of these nanoparticles thanks to the Au nanostar part of the Janus nanoparticles that can be further amplified with the use of magnetic concentration, allowing nanomolar detection in very small sample volumes. Furthermore, with the use of combined gold and iron oxide in a Janus configuration we demonstrate how these magnetoplasmonic nanoparticles act as superior contrast agents in a high variety of imaging techniques, including cell imaging in dark and bright field, multiplexed SERS mapping and 3D tomography in magnetic resonance imaging (MRI) and computed tomography (CT) among others.
[1] Reguera et al.; Synthesis of Janus plasmonic–magnetic, star–sphere nanoparticles, and their application in SERS detection, Farad. Discuss., 191, (2016) 47.
[2] Reguera et al.; Janus plasmonic-magnetic gold-iron oxide nanoparticles as contrast agents for multimodal imaging, Nanoscale 9, (2017) 9467.
2:15 PM - NM07.08.03
Design of Phage-Templated Gold Aggregates as Contrast Agents
Esen Sokullu 1 , Jiawei Zhang 1 , Gitanjali Kolhatkar 1 , Nedgine Laurenceau 1 , Maxime Pinsard 1 , Philippe Lassonde 1 , Francois Legare 1 , Andreas Ruediger 1 , Tsuneyuki Ozaki 1 , Marc Gauthier 1
1 , Institut National de la Recherche Scientifique (INRS), Varennes, Quebec, Canada
Show AbstractThe structure and properties of nanomaterials can be different for their ensembles compared to individual nanoparticles (NP) and corresponding bulk materials. Recently, self-assembly has emerged as a powerful technique to create organized nanostructures showing remarkable collective properties. In particular, ensembles of metallic NPs gain great attention as they are used to construct plasmonic nanostructures with enhanced optical properties depending on their geometry and the strength of the electromagnetic coupling. Due to the strong field localization, these nanostructures find applications in sensing, surface-enhanced spectroscopies, and nonlinear optics. Unlike the traditional top-down processes such as electron-beam lithography, self-assembly provides a versatile and low-cost fabrication route for complex 2-dimensional and 3-dimensional plasmonic nanostructures. Template-assisted assembly is a self-assembly approach whereas NPs are arranged into structures predefined by the shape of the templates. In this work, M13 and T4 phages were used as templates to create well-defined gold aggregates with two distinct geometry and size. Gold NP self-assembly was directed by displaying molecular recognition moieties on the phage surface which allowed control on the number of functional moieties at the genetic level. Thanks to the exceptional symmetry, identical mono-dispersed size, and shape of phage particles, gold NPs were deposited on phages with precise interparticle distance. Three different gold NP sizes (3 nm, 9 nm, and 13 nm) were employed to create gold aggregates and the effect of particle size on electric field enhancement was studied. Surface enhanced Raman scattering (SERS) studies showed that only 13 nm gold NPs were able to generate Raman signal. The Raman spectrum originated mainly from the surface of the gold NPs, within the interparticle nanogaps. Assembly of gold NPs on phage templates created nanogaps resulting in plasmonic near-field enhancement associated with collective plasmon modes of the aggregates. Raman signal enhancement of M13-templated gold aggregates was higher than the enhancement for T4-templated gold aggregates. It was due to the close proximity of gold binding moieties on phage surface and resulting close interparticle distance of gold particles. Plasmonic properties of phage-templated gold aggregates were also investigated by multiphoton photoluminescence (MPPL) microscopy. Similar results were observed. Gold aggregates assembled on M13 phage had higher multiphoton emission efficiency. However, unlike SERS, it was possible to observe MPPL emission with gold aggregates made of not only 13 nm NPs but also 9 nm gold NPs. Although the ability of generating intense photoluminescence with small gold NP size (9 nm) makes MPPL a good candidate for in vivo bioimaging applications, the observed higher enhancement factors make SERS a better candidate with higher sensitivity for biosensing.
3:30 PM - *NM07.08.04
Probing Chiral Biomolecules with Plasmonic Nanocrystals
Alexander Govorov 1 , Lucas Besteiro 1 , Xiang-Tian Kong 1
1 , Ohio University, Athens, Ohio, United States
Show AbstractOptical spectroscopies have the ability to reveal structural and chiral properties of molecular and nanoscale objects. About ten years ago, a new field of research – plasmon-based circular dichroism (CD) – was established and now it is a very active and rapidly-developing field of nanobiotechnology [1]. When a system includes both chiral biomolecules and plasmonic nanocrystals, the Coulomb and electromagnetic interactions between excitons and plasmons can alter and enhance the CD signals of the chiral molecular dipoles [2,3,4]. Especially strong enhancement factors for the molecular CD signals can be achieved using plasmonic hot spots and UV plasmons [3,4,5]. Strong CD signals can also appear in purely plasmonic systems with a chiral geometry and a strong particle-particle interaction [6,7,8]. Strongly-absorbing semiconductor nanocrystals, when grown using chiral biomolecules, also exhibit strong CD [9]. Our theoretical approaches treat the electromagnetic interactions in chiral plasmonic bio-assemblies using both classical and quantum formalisms and predict several novel mechanisms to both transfer and induce strong CD signal in the visible spectrum. Potential applications of chiral nano-assemblies are in bio-sensors and asymmetric chemistry.
[1] A. Cecconello, L.V. Besteiro, A.O. Govorov, I. Willner, Nat. Rev. Mat., in press (2017).
[2] A. O. Govorov, F. Zhiyuan, P. Hernandez, J.M. Slocik, and R. R. Naik, Nano Lett. 10, 1374 (2010).
[3] H. Zhang and A.O. Govorov, Phys. Rev. B 87, 075410 (2013).
[4] A. Ben-Moshe, B.M. Maoz, A.O. Govorov, G. Markovich, Chem. Soc. Rev. 42, 7028 (2013).
[5] L.V. Besteiro, H. Zhang, J. Plain, G. Markovich, Z. Wang, A.O. Govorov, Adv. Opt. Mat. DOI:10.1002/adom.201700069 (2017)
[6] Z. Fan, A.O. Govorov, Nano Lett. 10, 2580 (2010).
[7] A. Kuzyk, R. Schreiber, Z. Fan, G. Pardatscher, E.-M. Roller, A. Högele, F.C. Simmel, A. O. Govorov, T. Liedl, Nature 483, 311 (2012).
[8] A. Kuzyk, R. Schreiber, H. Zhang, A.O. Govorov, T. Liedl, N. Liu, Nat. Mater. 13,Pages: 862 (2014).
[9] A. Ben-Moshe, S.G. Wolf, M. Bar Sadan, L. Houben, Z. Fan, A.O. Govorov, G. Markovich, Nat. Commun. 5, 4302 (2014).
4:00 PM - *NM07.08.05
Computational Electrodynamics—A Powerful Tool for Nanophotonics and Microscopy
Lora Ramunno 1 , Antonino Cala' Lesina 1 , Jarno van der Kolk 1 , Pierre Berini 1
1 , University of Ottawa, Ottawa, Ontario, Canada
Show AbstractComputational electrodynamics simulations provide a critical complement to experimental investigations for understanding light matter interaction of complex systems. Its success is due in part to its relative simplicity and ease of use, coupled with its broad applicability to many material systems and optical processes. In this talk I will review the basic framework for the technique, its advantages and disadvantages, and highlight applications from our work relevant to this symposium. First I will discuss our recent work in nanophotonics. While computational electrodynamics has been, and continues to be, very widely used in plasmonics, there are significant issues in convergence and accuracy, which we have studied in detail, and which sometimes point to the need for parallel computing. With access to large computational resources, we are able to study complex arrangements of plasmonic objects, including multiple nanoparticle distributions for colour production. Second, I will discuss our computational electrodynamics simulations of nonlinear optical microscopy experiments. Our tool includes high numerical aperture light sources, propagation through heterogeneous media, nonlinear near-field interaction, subsequent propagation to the far field, and integration over a collecting lens. We have used this to unravel the image formation mechanisms in nonlinear optical microscopy, such as CARS, SRS and SHG microscopy. We find that the images are not a one-to-one density map of the object, but rather that the sub-micrometer to nanometer structure of the object, along with the coherence of parametric nonlinear optical processes, can be imprinted in the image in surprising ways.
4:30 PM - NM07.08.06
Nanoscopic Control and Quantification of Enantioselective Optical Forces
Yang Zhao 1 , Amr. A.E. Saleh 1 2 , Marie Anne van de Haar 3 , Keino Davis 1 , Brian Baum 1 , Justin Briggs 4 , Alice Lay 4 , Olivia Alexandra Reyes-Becerra 1 , Jennifer Dionne 1
1 Department of Materials Science and Engineering, Stanford University, Stanford, California, United States, 2 Department of Engineering Mathematics and Physics, Faculty of Engineering, Giza Egypt, 3 , FOM Institute AMOLF, Amsterdam Netherlands, 4 Department of Applied Physics, Stanford University, Stanford, California, United States
Show AbstractChirality is fundamental to many physical, chemical and biological systems, impacting processes as diverse as pharmaceutical drug-cell interactions and the evolution of snail colonies. However, controlling the assembly and separation of chiral molecules is extremely challenging and generally inefficient, particularly using prevailing chemical methods. Polarized light provides an alternative route towards enantio-selectivity, but these chiral-optical forces are usually too weak to be of practical use, and are also exceedingly challenging to both control and quantify, particularly for nano-specimens. The ability to enhance and quantitatively map enantioselective optical forces has the potential to not only improve our fundamental understanding of chiral light-matter interactions, but also enable new methods for chiral separation and assembly of chiral nanostructures. Here we demonstrate a new technique to both visualize and enhance these enantioselective forces. Using an achiral coaxial plasmonic nano-aperture and a nano-patterned chiral atomic force microscopy tip, we show that optical forces are highly dependent on the handedness of the illumination as well as the chirality of the probe. These plasmonic nano-apertures are composed of a deeply subwavelength circular dielectric channel embedded in a conducting film and can stably trap sub-20-nm dielectric chiral specimens. First, using both full-field simulations and analytic calculations, we show that selective trapping of enantiomers can be achieved with circularly polarized illumination. Opposite enantiomers experience distinct trapping forces in both sign and magnitude: one is trapped in a potential well down to -10kT at room temperature while the other is repelled with a potential barrier. These potentials maintain opposite signs across a range of chiral polarizabilities and enantiomer-aperture separations. Second, we demonstrate the first experimental mapping of the near-field chiral optical forces of a plasmonic nano-structure using a nano-patterned chiral atomic force microscopy tip. In particular, the total optical forces exerted on a left-handed chiral structure are more than 10pN stronger when illuminated with left- circularly polarized light (CPL) than with right-CPL; additionally, the transverse optical forces are attractive with left-CPL but repulsive with right-CPL. Third, we investigate enantioselective optical forces directly on chiral molecules exerted by the plasmonic nano-aperture, through functionalization of an achiral atomic force microscopy tip with DNA. We report the real-time monitoring of the morphological changes of DNA via changes in the enantioselective optical forces. This work paves the way toward sensitive probing of chiral light-matter interactions using plasmonic devices.
Symposium Organizers
Eva Hemmer, University of Ottawa
Niko Hildebrandt, Université de Paris Sud
Jianghong Rao, Stanford University School of Medicine
Fiorenzo Vetrone, University of Quebec-Instutitut National de la Recherche Scientifique
Symposium Support
ACS Nano | ACS Publications
ACS Photonics | ACS Publications
MilliporeSigma (Sigma-Aldrich Materials Science)
Photon etc
NM07.09: Lanthanide-Based Bioprobes—Near-Infrared Emitters
Session Chairs
Niko Hildebrandt
Ute Resch-Genger
Thursday AM, November 30, 2017
Hynes, Level 3, Room 308
8:30 AM - NM07.09.01
Deep Tissue Imaging with Highly Fluorescent NIR Nanocrystals after Systematic Host Screening
Pascal Gschwend 1 , Fabian Starsich 1 , Sotiris Pratsinis 1 , Rachel Grange 1 , Anton Sergeyev 1
1 , ETH Zurich, Zurich Switzerland
Show AbstractPhotoluminescent inorganic nanoparticles are attractive as bio-imaging contrast agents because they do not degrade by photobleaching and do not suffer from concentration quenching, such as clinically applied organic dyes. Here, for the first time, oxide, phosphate and vanadate nanocrystals doped with Nd3+ are systematically examined as down-converting photoluminescent contrast agents for bio-imaging in the near-infrared (NIR) window, where absorption and scattering by human tissue are reduced drastically. Through close control of their crystal size, the resulting fluorescence properties are quantitatively compared under NIR excitation. Most interestingly, contradicting to theoretical studies, no clear dependency on host crystal parameters could be found. However, BiVO4 doped with Nd3+ is revealed as the most efficient composition. Its application as photoluminescent NIR imaging contrast agent is demonstrated ex vivo with chicken skeletal muscle and bovine liver tissues. Under harmless laser power density (0.2 W/cm2), fluorescent BiVO4 particles could be clearly detected at an injection depth of up to 20 mm by a commercial camera.
8:45 AM - *NM07.09.02
Materials for Biophotonics in OTN-NIR Wavelength Region (Second Biological Window)
Kohei Soga 1 2 , Gil Yeroslavsky 1 2 , Masakazu Umezawa 1 , Masao Kamimura 1 2 , Laura Wortmann 1
1 Department of Materials Science and Technology, Tokyo University of Science, Tokyo Japan, 2 Imaging Frontier Center, Tokyo University of Science, Noda, Chiba, Japan
Show AbstractOver-1000-nm (OTN) near infrared (NIR) wavelength region, or second biological window, is known to be that with minimal optical loss for optical transparency of biological tissues. The major reasons of the loss are absorption and scattering. The absorption loss can possibly be avoided by applying higher sensitivity of the image capturing device or using the more intense light source. However, since the scattering causes haze the image, which is also intensified by the above improvement, it is more serious loss problem than the absorption. The major scattering is caused by the refraction and reflection at refractive index gap to bend the direction of light. Due to larger difference of the refractive index in shorter wavelength, the shorter the wavelength is, the stronger the scattering. This fact draws researchers of imaging to longer and longer wavelength. Also, it is of cause better avoiding the very strong absorption in middle infrared by the molecular vibration. The authors have studied to apply the transparency of the OTN-NIR for biophotonics since 2005. The paper will review the nanostructure development of the materials with photonic function for the OTN-NIR biophotonics. The topics will cover normal fluorescent probes, photodynamic therapy and nanothermometry by using the OTN-NIR excitation light source.
9:15 AM - *NM07.09.03
NIR Nanomaterials for Disease Diagnostics and Therapy
Fan Zhang 1
1 , Fudan University, Shanghai China
Show AbstractUpconverting nanoparticles (UCNPs) present a new technology for optical imaging/detection which is a growing field with both diagnostic and drug discovery uses. Currently, fluorophores including fluorescent dyes/proteins and quantum dots (QDs) are used for fluorescence-based imaging and detection. These are based on ‘downconversion fluorescence’, emitting low energy fluorescence when excited by high energy light (such as UV or short wavelength visible light). Fluorophores in current use have several drawbacks: photobleaching, autofluorescence, short tissue penetration depth and tissue photo-damage. UCNPs emit detectable photons of higher energy in the visible range upon irradiation with near-infrared (NIR) light based on a process termed ‘upconversion’. UCNPs show absolute photostability, negligible autofluorescence, high penetration depth and minimum photodamage to biological tissues. They can be used for ultrasensitive interference-free biodetection because most biomolecules do not have upconversion properties.
Acknowledgements
The work was supported by NSFC (grant No. 21322508), China National Key Basic Research Program (973 Project) (No. 2013CB934100, 2012CB224805).
References
R. Wang, L. Zhou, W. X. Wang, X. M. Li, F. Zhang*. Nature.Comm., 8, 14702 (2017)
C. Yao, X. M. Li, and F. Zhang*, Adv. Mater., 28, 9341 (2016)
L. Zhou, R. Wang, C. Yao, X. M. Li, D. Y. Zhao and F. Zhang*, Nature.Comm., 6, 6938 (2015)
X. M. Li, F. Zhang*, and D. Y. Zhao Chem. Soc. Rev., 44, 1346 (2015)
R. Wang, X. M. Li, L. Zhou and F. Zhang*, Angewand.Chem.Int. Ed., 53, 12068 (2014)
L. Chen, L. Zhou, D. Zhu, C. H. Fan and F. Zhang*, Anal. Chem., 87, 1346 (2015)
X. M. Li, R. Wang, F. Zhang* and D. Y. Zhao*, Nano. Lett., 14, 3634 (2014)
C. Yao, X. M. Li, D. Y. Zhao and F. Zhang*, Anal. Chem., 86, 9749 (2014)
F. Zhang*, R. C. Che, P. Hu, et. al, Nano. Lett., 12, 2852 (2012)
NM07.10: Lanthanide-Based Bioprobes—Sensors I
Session Chairs
Niko Hildebrandt
Fan Zhang
Thursday PM, November 30, 2017
Hynes, Level 3, Room 308
10:15 AM - *NM07.10.02
Near-Infrared Optical Nanoprobes for Biomedical Applications—Light and Heat Complex Marriage
Antonio Benayas 1 2
1 , Stanford School of Medicine, Stanford, California, United States, 2 , CICECO-University of Aveiro, Aveiro Portugal
Show AbstractBiomedical luminescence imaging and sensing, especially when carried out using light-emitting nanoprobes as contrast agents, enables the study of rapid biological processes in greater detail than is currently achievable with other imaging modalities, such as magnetic resonance imaging (MRI), ultrasound and computed tomography. Results discussed in this work are framed into the current trend of developing systems absorbing/emitting near-infrared (NIR) wavelengths falling into the "biological windows" (BWs) of optical transparency of tissues, thus improving penetration depth and optical contrast of nanoparticle-driven luminescence imaging. One interesting kind of luminescence-based sensing is nanothermometry, as a non-invasive way for an early detection of health perturbations causing temperature variations. All-optical nanothermometers also offer the potential of real-time monitoring during thermal treatment of diverse diseases.
Moreover, as the optical excitation absorbed by these all-optical mentioned above nanoprobes is not entirely converted into a light signal -at a different wavelength-, some interesting opportunities can be found for using the exceeding amount of optical excitation, in the form of heat, for others modalities of imaging (photoacoustic), or photothermal therapy purposes.
The set of results discussed in this work cover different kind of materials such as quantum dots and lanthanide-doped nanoparticles, being the scope multi-pronged, built up around the interrelation of light and heat in that aforementioned context. First, high-brightness nanoprobes emitting in the BWs bring the opportunity to carry out low-dose in vivo imaging, with no noticeable toxicity. Second, we analyze the expansion of the spectral range of action, further into NIR range, of recently developed luminescent nanothermometers, remarkably valid to work in aqueous solutions.
As a third separate block, we tackle how our systems originally aiming for light-to-light conversion can effectively deliver heat as well, in an optically controlled, local manner. The great additional advantage is that we apply luminescence nanothermometry for a real-time in situ monitoring of the induced temperature change, with a much better accurate sub-skin readout than other alternative methods like thermal cameras.
(Finally, a general prospective in photoacoustic imaging and heat at the nanoscale might be given, depending on the progress of research lines, that are currently ongoing at the time of writing this abstract).
10:45 AM - *NM07.10.03
In Vivo Imaging of Intercellular Forces with Strain-Sensitive Upconverting Nanoparticles
Jennifer Dionne 1
1 Materials Science and Engineering, Stanford University, Stanford, California, United States
Show AbstractCells and their constituents constantly push and pull on their surroundings, generating and sensing forces that dictate whether a cell is healthy or will become diseased. We experience these forces every time our heart beats, our ears hear, or a wound heals. Mechanical forces also affect gene expression, stem-cell differentiation, ion-channel gating, synaptic plasticity, and tissue organization. Despite the prevalence and significance of biological forces, few tools exist to directly measure these forces, and instead rely on biochemical, molecular, or genetic information to infer biological function and fate. This presentation will describe our group’s efforts to develop a new class of in vivo force probes to monitor picoNewton to microNewton biological forces with extremely high spatial and temporal resolution. Our design is based on inorganic nanoparticles that, when excited in the near-infrared, emit light of a different (visible) color and intensity in response to compressive stress. The nanoparticles are small, bio-compatible, do not bleach or photoblink, need not be genetically encoded, and, by virtue of their infrared absorption, can enable deep tissue imaging with minimal tissue autofluorescence and light-induced tissue damage. We deploy these upconverting nanoparticles in C. elegans to generate high-resolution in vivo force maps. In particular, we focus on the forces generated by these tiny roundworms as they feed and digest their bacterial food, to visualize how digestive tract forces vary across space and time. These force measurements are coupled with electrical measurements of muscle contractions in both wild-type and mutant animals, providing insight into the interplay between mechanical, electrical, and chemical signaling in vivo.
11:15 AM - NM07.10.04
Ratiometric Imaging of Endogenous Hypochlorous Acid in the Second Near-Infrared Window beyond 1500 nm
Shangfeng Wang 1
1 , Fudan University, Shanghai China
Show AbstractDeveloping fluorescent probes for visualizing reactive oxygen species (ROS) in vivo is imperative to both understanding the precise roles of ROS in many life-threatening diseases and optimizing therapeutic interventions. However, the currently available fluorescent probes have emission limited to fluorescence channels in the visible and first near-infrared (NIR-I; ∼700–900 nm) spectral regions, which are unsuitable for deep-tissue high-resolution optical imaging because of scattering photons and background autofluorescence. We herein report a fluorescent nanoprobe for the ratiometric detection of hypochlorous acid (HOCl) in the second near-infrared window (NIR-II; ∼1000–1700 nm) of lanthanide-based downconversion nanoparticle beyond 1500 nm. Specifically, downconversion luminescence excited under 808 nm can be effectively quenched by the Cy7.5 chromophores on the surface of nanoparticles via an absorption competition process and subsequently recovered upon the addition of HClO, while downconversion luminescence excited under 980 nm remains unchanged in the whole process, thus allowing for ratiometric and quantitative monitoring of HClO. Optical phantom experiments confirm the advantages of the NIR-II probe over conventional dyes in the first near-infrared region. This study provides a new design strategies of NIR-II fluorescent probes for precise and reliable measurement in biological systems.
NM07.11: Lanthanide-Based Bioprobes—Sensors II
Session Chairs
Antonio Benayas
Jianghong Rao
Thursday PM, November 30, 2017
Hynes, Level 3, Room 308
1:30 PM - NM07.11.01
In Vivo Application of Upconverting Force Sensors to Elucidate Neuromuscular Pump Action in C. elegans
Alice Lay 1 , Alakananda Das 1 , Christopher Siefe 1 , Holger Fehlauer 1 , Derek Wang 1 , Miriam Goodman 1 , Jennifer Dionne 1
1 , Stanford University, Stanford, California, United States
Show AbstractThe feeding behavior of C. elegans is a strong indicator of health; changes indicate environmental toxins, scarce or abundant food resources, aging, and neurodegenerative disease. In particular, the pharyngeal pump action is a rhythmic contraction and relaxation of muscles that allows the worm to pull in and concentrate bacteria, crush and chew them in the grinder, and then pass them through the intestinal tract [1]. Because the pump action is regulated by motor neurons (MC, M3, M4) [2-5], it serves as a model system for neuromuscular pumps like the heart. Here, we investigate the magnitude of forces exerted by muscles in the pharynx, combining extracellular electrophysiological recordings, or electrophargyngograms (EPGs), with optical force measurements from upconverting nanoparticles (UCNPs). Sub-25 nm Mn2+-doped NaYF4:Er,Yb UCNPs provide a photostable and consistent color response to stress [6]. The nano- to micro-Newton sensitivity of these nanoparticles relies on the energetic coupling between the crystal field sensitive d-metal and upconverting lanthanides, which under stress, yields a positive or negative change in the red to green Er3+ emission ratio for cubic- and hexagonal-phase NaYF4, respectively. We demonstrate the first in vivo capabilities of these nanosensors to image and quantify forces exerted along the pharynx. First, we incubate the worms with water-soluble UCNPs (5 mg/mL) overnight for feeding. Then, we load the worms in a microfluidic device and collect upconversion spectra at key anatomical features. Based on ratiometric differences in emission peaks, we find that forces exerted in the grinder (~10 uN) are nearly an order of magnitude higher than those exerted at the pharyngeal-intestinal valve (~1 uN). Furthermore, we compare these optical force measurements to muscle contraction and relaxation events, characterized by voltage spikes in the EPGs. We determine pump action parameters (e.g., duration, frequency, amplitude) and muscular forces in wild-type and neurotransmitter-treated (5 mM serotonin) worms. From these results, we work towards mapping neuromuscular pump dynamics and providing the first in-vivo determination of the forces required for healthy function in C. elegans.
[1] Fang-Yen, C., L. Avery, and S. Aravinthan. PNAS (2009)
[2] Raizen, D.M. and L. Avery. Neuron (1994)
[3] Niacaris, T. and L. Avery. Journal of Experimental Biology (2003)
[4] Trojanowski, N.F., D.M. Raizen, and C. Fang-Yen. Scientific reports (2016)
[5] Lee, K.S. et al. Nature Communications (2017)
[6] Lay, A. et al. Nano Letters (2017)
1:45 PM - NM07.11.02
Photoluminescence Lifetime of Single Upconversion Nanowire near an Interface
Xuezhe Zhou 1 , Matthew Lim 1 , Xiaojing Xia 1 , Peter Pauzauskie 1
1 , University of Washington, Seattle, Washington, United States
Show AbstractDevelopment of practical upconversion nanocrystals for bio-imaging and bio-sensing requires the understanding of radiative and nonradiative emission rates under different conditions and environments. In this work, photoluminescence lifetime of the single rare-earth-doped-sodium-yttrium-fluoride nanowire in water is measured as a function of the distance between the nanowire and substrate at various temperatures. We use optical tweezers to precisely control the individual nanowire’s position away from the substrate in the temperature controlled chamber. We discover a strong dependence of the lifetime relative to the distance and temperature changes. The nanowire far from the substrate exhibit a much longer lifetime than the lifetime of nanowire on the substrate, which is due to the emitting dipoles’ local density of states variation. In addition, the lifetime of nanowires embedded polydimethylsiloxane composite is studied as a function of temperature and laser irradiance, which shows the potential applications in controlling and probing temperature in nanoscale for photothermal therapy and bio-sensing.
NM07.12: Nano-Biointeraction
Session Chairs
Antonio Benayas
Jianghong Rao
Thursday PM, November 30, 2017
Hynes, Level 3, Room 308
2:00 PM - *NM07.12.01
Analytical Ultracentrifugation Studies of Nanoparticles/Protein Interactions
Ahmet Bekdemir 1 , Francesco Stellacci 1
1 , EPFL, Lausanne Switzerland
Show AbstractIt has become apparent that a large part of the interactions between nanopartilces and biological media is mediated by the protein corona that surrounds the former. It remains less clear how to treat the complexity of a nanoparticle surrounded by many proteins that compete to occupy its surface. Recently, we have shown that it is possible to derive the basic thermodynamic variable that rule the interactions of a single protein with a single nanoparticles.
In this talk, the basics of the use of analytical ultracentrifugation (AUC) for the determination of the interactions between BSA and monodisperse particles will be highlighted. The use of these findings as foundation for more complex studies will also be presented.
2:30 PM - NM07.12.02
Effect of the Protein Corona in Nanoparticle-Assisted Lateral Flow Immunoassays for the Detection of Zika
Helena de Puig Guixe 1 , Irene Bosch 1 , Marc Carré Camps 1 , Lee Gehrke 1 , Kimberly Hamad-Schifferli 1
1 , MIT, Cambridge, Massachusetts, United States
Show AbstractLateral flow devices are ideal candidates to diagnose diseases in remote areas because they can be operated by non-experts, are cheap, portable, and do not require electric power to be operated. We present results on a machine-readable lateral flow device for the detection of Zika. The device relies on a lateral flow immunoassay, which uses capillary flow and the accumulation of ligand-coated nanoparticles to detect the presence of target proteins. We investigate the effect of the protein corona on the function of nanoparticle antibody conjugates. Antibodies specific for Zika virus nonstructural protein 1 (NS1) are conjugated to gold nanoparticles both covalently and by passive absorption, and another anti-NS1 antibody is immobilized onto the nitrocellulose membrane. We engineer the nanoparticle shape, size, surface chemistry, and biofunctionalization in order to lower the overall detection limit of the device, and study the interactions of proteins on the overall performance of the immunoassay. The nanoparticle surface properties and biofunctionalization are characterized by gel electrophoresis, DLS, and fluorescence/optical spectroscopy in conjunction with chemical displacement.
Sandwich immunoassay formation is influenced by whether the strip is run in corona forming conditions, i.e., in human serum. Strips run in buffer or pure solutions of bovine serum albumin exhibit false positives, but those run in human serum do not. Serum pretreatment of the nitrocellulose also eliminates false positives. Corona formation around the NP-Ab in serum is faster than the immunoassay timescale. Langmuir binding analysis determines how the immobilized Ab affinity for the NP-Ab/NS1 is impacted by corona formation conditions, quantified as an effective dissociation constant, KDeff. Results show that corona formation mediates the specificity and sensitivity of the antibody-antigen interaction of Zika biomarkers in immunoassays.
Limit of detection, as well as sensitivity/specificity are critical issues in the development of rapid diagnostics; these parameters are dependent on the nature of the ligand-target pair, protein corona forming conditions, as well as binding thermodynamics when attached on a surface. I explore strategies to increase the sensitivity and specificity of the lateral flow devices. These new, effective, fast, reliable and inexpensive lateral flow devices represent significant improvements to field detection of disease and real-time epidemiology in situations where there is a lack of specialized personnel, reagents or materials challenge the suitability of the standard diagnosis methods.
2:45 PM - NM07.12.03
Immune Suppressing Hyaluronic Acid Coated Chitosan Nanoparticles
Abdulaziz Almalik 1 , Ali Alhasan 1
1 , King Abdulaziz City for Science and Technology, Riyadh Saudi Arabia
Show AbstractStudying the interactions of nanoparticles (NPs) with serum proteins is necessary for the rational development of nano-carriers. Optimum surface chemistry is a key consideration to modulate the formation of the serum protein corona (PC) and the resultant immune response. We investigated the constituent of the PC formed by hyaluronic acid-coated chitosan NPs (HA-CS NPs). Non-decorated chitosan NPs (CS NPs) and alginate-coated chitosan NPs (Alg-CS NPs) were utilized as controls. Results show that HA surface modifications significantly reduced protein adsorption relative to controls. Gene Ontology (GO) analysis demonstrates that HA-CS NPs were the least immunogenic nano-carries. Indeed, less inflammatory proteins were adsorbed onto HA-CS NPs as opposed to CS and Alg-CS NPs. Interestingly, HA-CS NPs differentially adsorbed two unique anti-inflammatory proteins, which were absent from the PC of both controls. On the other hand, CS and Alg-CS NPs selectively adsorbed a proinflammatory protein that was not found on the surfaces of HA-CS NPs. Our results suggest that our two unique anti-inflammatory proteins can be used to modulate the interaction of NPs with the host immune system to potentially reduce the immunogenicity of a wide range of nanomaterials.
NM07.13: Magnetic and Multimodular Bioprobes
Session Chairs
Jianghong Rao
Adam Shuhendler
Thursday PM, November 30, 2017
Hynes, Level 3, Room 308
3:30 PM - NM07.13.01
Non-Cytotoxic Smart Core/Shell Nanoparticles and Their Application in Nanomedicine
Zied Ferjaoui 1 2 , Raphael Schneider 1 , Abdelaziz Meftah 2 , Eric Gaffer 1 , Halima Alem 1
1 , Lorraine University, Nancy France, 2 , Faculté des Sciences de Tunis, Tunis Tunisia
Show AbstractOne of the major challenges in nanomedicine is to develop nanoparticulate systems able to serve as efficient diagnostic and/or therapeutic tools against sever diseases, such as infectious or neurodegenerative disorders. To enhance the detection and interpretation contrast agents were developed to increase the signal/noise ratio. Among them, Superparamagnetic Iron Oxide (SPIO) and Quantum Dots (QDs) nanoparticles (NPs) have received a great attention since their development as a liver contrasting agent 20 years ago for the SPIO. Furthermore, their properties, originating from the nanosized dimension and shape, allow different biodistribution and opportunities beyond the conventional chemical imaging agents3. The opportunity to coat those biocompatible NPs by a polymer shell that can ensure a better stability of the materials in the body, enhance their biodistribution and give them new functionalities appears as very challenging for medicinal applications. In this work, we have developed new responsive SPIO and QDs based NPs that are able to carry the anticancer drug doxorubicin (DOX) and release it in physiological media and at the physiological temperature. Two family of nanoparticles were synthesized, the first one consist in superparamagnetic Fe3O4 NPs that were functionalized by a biocompatible responsive copolymer based on 2-(2-methoxy) ethyl methacrylate (MEO2MA), oligo (ethylene glycol) methacrylate (OEGMA). The second family consists in the ZnO nanoparticles coated by the same copolymer. For the first time, P(MEO2MAx-OEGMAy) was grown by activator regenerated by electron transfer–atom radical polymerization (ARGET-ATRP) from the NPs surfaces by surface-initiated polymerization4. The core/shell NPs were fully characterized by the combination spectroscopic and microscopic techniques. We demonstrate the efficiency of the ARGET-ATRP process to graft polymers and copolymers at the surface of Fe3O4 and ZnO NPs. The influence of the polymer chain configuration (which leads to the aggregation of the NPs above the collapse temperature of the copolymer (LCST)) was studied. We demonstrate that the magnetic properties of the core/shell Fe3O4-based nanostructures were only influenced by the amount of the grafted polymer and no influence on the aggregation was evidenced4. This simple and fast process developed is efficient for the grafting of various co-polymers from any surfaces and the derived nanostructured materials display the combination of the physical properties of the core and the macromolecular behavior of the shell. The drug release experiments confirmed that DOX was largely released above the co-polymer LCST. Moreover, the cytocompatibility test showed that those developed nanoparticles do not display any cytotoxicity depending on their concentration in physiological media. From the results obtained, it can be concluded that the new nanomaterials developed can be considered for further use as multi-modal cancer therapy tools.
3:45 PM - NM07.13.02
MRI Dual (T1-T2) Contrast Modality of Truncated Nanocubic Iron Oxides with High Stability and Cellular Internalization
Bibek Thapa 1 2 , Daysi Diaz-Diestra 7 , Nitu Kumar 6 , Huadong Zeng 3 , Juan Beltran-Huarac 8 , Brad Weiner 4 , Gerardo Morell 5
1 , University of Puerto Rico, San Juan, Puerto Rico, United States, 2 , Molecular Sciences Research Center, San Juan, Puerto Rico, United States, 7 Chemistry, University of Puerto Rico at Río Piedras, San Juan, Puerto Rico, United States, 6 , University of Puerto Rico at Río Piedras, San Juan, Puerto Rico, United States, 3 , University of Florida, Gainesville, Florida, United States, 8 , Harvard T Chan School of Public Health, Boston, Massachusetts, United States, 4 Chemistry, University of Puerto Rico at Río Piedras, San Juan, Puerto Rico, United States, 5 Physics, University of Puerto Rico at Río Piedras, San Juan, Puerto Rico, United States
Show AbstractThe superior performance magnetic resonance imaging (MRI) diagnosis necessitates the elevated magnetic resonance (MR) relaxivity of the contrast nanoprobes accompanied by their efficient cellular internalization. The conventional single imaging modality of nanoparticles-based contrast probe precipitates the false imaging in MRI, and hence, the development of dual-imaging, T1- and T2-weighted, modality could afford accurate imaging and diagnosis. In this study, we demonstrate nitrodopamine-PEG (ND-PEG) grafted truncated nanocubic iron oxides (tNCIOs) capable of inducing simultaneous dual longitudinal and transverse relaxivities, and the values are observed to be staggeringly elevated 32 and 791 mM-1Sec-1 respectively. The resulted nanocubes (ND-PEG-tNCIOs) show high stability in the physiological media. The in vitro testing reveals the higher cellular internalization of fluorescent dye—Alexa555 conjugated ND-PEG-tNCIOs in the human non-phagocytic cells, CCRF-CEM and HeLa while very minimal internalization in the phagocytic cells, the peripheral blood macrophages—CRL 9855. This observation is suggestive of tumor recognition and immune evasive capability of the resulted nanocubes. This strategy and the outcomes offer an important foundation for the precise detection of high-risk cancer tumors by MRI at high sensitivity and spatial resolution.
4:00 PM - *NM07.13.03
You Can Run, But You Can't Aldehyde—Tracking an Elusive Biomolecule with Imaging
Adam Shuhendler 1 2
1 Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada, 2 , University of Ottawa Heart Institute, Ottawa, Ontario, Canada
Show AbstractReactive carbonyls, including aldehydes, are regularly produced in cells through both anabolic and catabolic processes necessary for life. The production of aldehydes is tightly regulated, maintaining low homeostatic concentrations required for immune responses, genetic regulation, and signal transduction mechanisms. Chemical or physical stress on our cells can throw aldehyde levels into dysregulation. The formation of aldehydes often marks prodromal phases of disease initiation, and their levels have been associated with the prognosis of atherosclerosis and cancer, and they have been proposed to be the molecular culprits of an array of drug induced liver injury. Furthermore, hypotheses of ‘aldehyde load’ exist in neurodegenerative disease and across the spectrum of brain injury. The non-invasive mapping of aldehydes in living systems has not yet been achieved, however there is an unexplored potential to access a novel early imaging biomarkers for injury and a variety of diseases. Additionally, while aldehydes have shown significant elevations in human body fluids, their detection often requires laborious sample preparation or advanced analytical techniques (e.g. mass spectrometry). In order to realize the potential of endogenously generated aldehydes for the diagnosis of a range of diseases and injuries, a rapid and simple point-of-care method of aldehyde identification is needed. Building upon previous work establishing rapid, catalyst-free trapping of aldehydes using N-amino anthranilic acids, we have developed chemical traps that selectively and rapidly complex aldehydes under physiological conditions. We are now taking steps to simultaneously realize the potential of aldehydes for medical imaging and point-of-care diagnostics. Towards in vivo imaging, we have developed activatable molecular MRI contrast agents providing imaging signal through chemical exchange saturation transfer (CEST). Our hydrazine-containing agents, collectively termed Hydrazo-CEST, are CEST-inactive until they trap reactive carbonyls to form hydrazones, allowing proton exchange from the ring-proximal nitrogen to produce high CEST-MRI contrast (%MTRasym>20%). Using a variety of control probes, we have identified the structural requirements for CEST signal production and have explored the effects of the electronics of both hydrazine and carbonyl components on signal generation. Towards point-of-care diagnostics, we have developed carboxylic acid or ester-modified N-amino anthranilates for aldehyde 'fingerprinting' in body fluids utilizing excitation-emission matrices and chemometric analyses. Through our chemical approach, we have begun to make aldehydes a viable target for translational imaging and point-of-care diagnostics, and will work to realize the full potential of these fundamental biomarkers of cell stress.
4:30 PM - NM07.13.04
Multimodal and Multifunctional Inorganic-Organic Hybrid Nanoparticles
Claus Feldmann 1
1 , Karlsruhe Institute of Technology (KIT), Karlsruhe Germany
Show AbstractMultimodular nanoparticles for medicine should comprise low material complexity, intense emission for optical imaging at high photostability and optional drug release at high drug load. Inorganic-organic hybrid nanoparticles (IOH-NPs) with a composition [ZrO]2+[RfunctionOPO3]2- [1-3] or [GdO]+[RfunctionSO3]- [3-5] combine these requirements ideally. The saline compounds consist of equimolar amounts of an inorganic cation (i.e., [ZrO]2+, [GdO]+) and a functional organic anion [RfunctionOPO3]2- or [RfunctionSO3]- (Rfunction: functional organic group). The essential role of the inorganic cation is to guarantee the insolubility of the IOH-NPs in water. It is to be noted that the load of the functional organic anion is extraordinarily high due to this specific composition (i.e. 70-85 wt-% of total IOH-NP weight).
Specific examples of IOH-NPs are, for instance, [ZrO]2+[PUP]2-, [ZrO]2+[MFP]2-, [ZrO]2+[RRP]2-, [ZrO]2+[DUT]2-, [GdO]+[AMA]– or [GdO]+[ICG]– that show blue, green, red and infrared fluorescence (PUP: phenylumbelliferon phosphate; MFP: methylfluorescein phosphate; RRP: resorufin phosphate; DUT: Dyomics-647 uridine triphosphate; AMA: amaranth red; ICG: indocyanine green) [2,3,5]. [GdO]+[ICG]– turned out as a novel, multi-modality contrast agent for optical (OI), photoacoustic (PAI) and magnetic resonance imaging (MRI) [5]. The high [ICG]– content (81 wt-%) ensures for intense near-infrared emission (780-840 nm) and a strong photoacoustic signal.
Besides fluorescence, the material concept can be expanded to drug transport and drug delivery including [ZrO]2+[BMP]2- and [ZrO]2+[FdUMP]2- with the anti-inflammatory agent betamethason phosphate (BMP) and the cytostatic agent 5’-fluoro-2’-deoxyuridine 5’-monophosphate (FdUMP) [2-4]. In vitro and in vivo studies confirm excellent activity and high biocompatibility. [ZrO]2+[BMP]2- shows an effective inflammatory response in vitro (i.e. MH-S macrophages) [1]. In vivo studies, furthermore, indicate a promising therapeutic efficacy in a mouse model of multiple sclerosis with an increased cell-type specificity compared to conventional free glucocorticoids [4]. In vitro studies with mammary carcinoma cells, moreover, show a strong anti-proliferative activity of [ZrO]2+[FdUMP]2- IOH-NPs, which was even prominently higher than the effect of clinically applied 5-fluorouracil [1].
[1] M. Roming, H. Lünsdorf, K. E. J. Dittmar, C. Feldmann, Angew. Chem. Int. Ed. 2010, 49, 632.
[2] J. G. Heck, J. Napp, S. Simonato, J. Möllmer, M. Lange, H. R. Reichardt, R. Staudt, F. Alves, C. Feldmann, J. Am. Chem. Soc. 2015, 137, 7329.
[3] J. Heck, M. Poß, J. Napp, W. Stühmer, H. M. Reichardt, F. Alves, C. Feldmann, DE 10 2014 004 512.9, WO 2015 144 282.
[4] E. Montes-Cobos, S. Ring, H. Fischer, J. Heck, M. Schwaninger, C. Feldmann, F. Lühder, H. M. Reichardt, J. Contr. Rel. 2017, 245, 157.
[5] M. Poß, R. J. Tower, J. Napp, L. C. Appold, T. Lammers, F. Alves, C.-C. Glüer, S. Boretius, C. Feldmann, Chem. Mater. 2017, 29, 3547.
4:45 PM - NM07.13.05
Targeted Multimodal Nanoparticles for Pre-Procedural MRI and Intra-Operative Image-Guidance
Joonseok Lee 1 2 , Wooram Park 3 , Elena Rozhkova 4 , Dong-Hyun Kim 3
1 , Korea Institute of Science and Technology, Seoul Korea (the Republic of), 2 Nano & Information Technology, KIST School, Seoul Korea (the Republic of), 3 Radiology, Northwestern University, Chocago, Illinois, United States, 4 CNM, Argonne National Laboratory, Lemont, Illinois, United States
Show AbstractMultimodal-imaging probes offer a novel approach, which can provide detail diagnostic information for the planning of image-guided therapies in clinical practice. Here we report targeted multimodal Nd3+-doped upconversion nanoparticle (UCNP) imaging reporters, integrating both magnetic resonance imaging (MRI) and real-time upconversion luminescence imaging (UCL) capabilities within a single platform. Nd3+-doped UCNPs were synthesized as a core–shell structure showing a bright visible emission upon excitation at the near infrared (minimizing biological overheating and increasing tissue penetration depth) as well as providing strong MRI T2 contrast (high r2/r1 ratio). Transcatheter intra-arterial infusion of Nd3+-doped UCNPs conjugated with anti-CD44-monoclonal antibody allowed for high performance in vivo multimodal UCL and MR imaging of hepatocellular carcinoma (HCC) in an orthotopic rat model. The resulted in vivo multimodal imaging of Nd3+ doped core-shell UCNPs combined with transcatheter intra-arterial targeting approaches successfully discriminated liver tumors from normal hepatic tissues in rats for surgical resection applications. The demonstrated multimodal UCL and MRI imaging capabilities of our multimodal UCNPs reporters suggest strong potential for in vivo visualization of tumors and precise surgical guidance to fill the gap between pre-procedural imaging and intraoperative reality.
Symposium Organizers
Eva Hemmer, University of Ottawa
Niko Hildebrandt, Université de Paris Sud
Jianghong Rao, Stanford University School of Medicine
Fiorenzo Vetrone, University of Quebec-Instutitut National de la Recherche Scientifique
Symposium Support
ACS Nano | ACS Publications
ACS Photonics | ACS Publications
MilliporeSigma (Sigma-Aldrich Materials Science)
Photon etc
NM07.14/NM06.13: Joint Session: Nanoparticle Bioprobes
Session Chairs
Jennifer Dionne
Eva Hemmer
Friday AM, December 01, 2017
Hynes, Level 3, Room 311
9:00 AM - *NM07.14.01/NM06.13.01
Gold Nanostar Probes for Imaging and Therapeutics
Teri Odom 1
1 , Northwestern University, Evanston, Illinois, United States
Show AbstractNanotechnology offers new strategies for minimally invasive and localized approaches to diagnose and treat diseases. Recently, nanoparticles have been explored in a range of applications, including as drug delivery vehicles, imaging probes, and therapeutic agents. Although increased therapeutic efficacy has been realized, direct visualization of how engineered nanoparticles interact with specific organelles or cellular components has seen limited attention. Such interactions will have implications for fundamentals in cancer biology as well as in design of translational therapeutic agents. This talk will describe how drug-loaded gold nanostars can behave as multi-spectral optical probes to interrogate how nanoconstructs interact with cancer cells at the nanoscale and how their shape can significantly boost magnetic resonance imaging (MRI) contrast signals.
9:30 AM - NM07.14.03/NM06.13.03
Ph-Sensitive Mesoporous Silica-Coated Gold Nanorods for Tumor-Triggered Uptake and Multifunctional Theranosis and Their Cellular Uptake Analysis at the Single Particle Level
Sungwook Jung 1 , Xiaoyuan Chen 1
1 LOMIN, NIH/NIBIB, Bethesda, Maryland, United States
Show AbstractMesoporous silica-based nanoparticles have garnered a great deal of attention as potential carriers with high drug capacity. However, blocking the non-specific releasing of drugs from the pores, achieving triggered drug release from the pores, and overcoming toxicity induced by silanol groups in vivo have been challenging. We synthesized mesoporous silica-coated gold nanorods (AuNRs) and loaded therapeutics, photosensitizer, into the pores using electrostatic interactions. The surface of mesoporous silica-coated AuNRs was modified by amino groups to hold back non-specific drug release from the pores. The amino-functionalization on the surface of AuNRs was monitored by Fourier transfer infrared spectrometer. The loading contents of photosensitizer reached up to 15.1%, which showed no significant change in cell medium for 24 h. We characterized drug-eluting properties in vitro of the pores and demonstrated that mesoporous silica-coated AuNRs released photosensitizers in response to the irradiation of near-infrared (NIR) light at a tumor site, resulting in cellular apoptosis. The cellular uptake pathway of mesoporous silica-coated AuNRs was monitored at the single particle level using total internal reflection fluorescence microscopy. We confirmed that the mesoporous silica-coated AuNRs bind to the cell membrane and subsequently clathrin-coated pits form at this site. The mesoporous silica-coated AuNRs were decorated by poly(ethylene glycol) (PEG), which blocks exposure of the silanol groups to surrounding and leads to a long-time circulation in vivo for the AuNRs to extravasate into tumors by enhanced penetration and retention effects. Because the PEG shell is formed on the surface of AuNRs through β-carboxylic amides which can be hydrolyzed in mildly acidic condition (~pH 6.5), the surface of AuNRs changed to positively charge and they were then readily internalized by tumor cells. The tumor region was detected by dual imaging modules; photoacoustic (PA) imaging by thermal expansion induced by AuNRs and positron emission tomography (PET) by 64Cu doping. PA signal by the AuNRs was higher by 2.5 times compared with the normal region, while in the PEG images we could detect the tumor uptake value increased up to 8.7% injected dose/g for 24 h. In the irradiation of NIR laser to the tumor, the AuNRs induced the PTT effects and simultaneously photosensitizers generated the singlet oxygens; this combination of PTT and photodynamic therapy removed synergistically the tumors as factor of 12. The combination of internal (pH)- and external (light)-stimuli in the nanoplatform can enable the programmable theranosis for the synergistic cancer nanomedicine.
9:45 AM - NM07.14/NM06.13
BREAK
10:15 AM - NM07.14.04/NM06.13.04
Investigation of the Use of Nanocrater-Decorated Anodic Aluminum Oxide Membranes as Substrates for Reproducibly Enhanced SERS Signals
Merve Celik 1 , Sevde Altuntas 1 , Fatih Buyukserin 1
1 , TOBB University of Economics and Technology, Ankara Turkey
Show AbstractSurface-enhanced Raman spectroscopy (SERS) is an optical phenomenon yielding enhanced Raman signals on nano decorated conducting materials. It provides label-free analysis of molecules and has the potential to detect down to single molecule.[1] Despite the potential sensitivity and the wide range of applications for SERS, it can not be used as a routine diagnostic tool due mainly to the poor reproducibility of the SERS signals with high intensities.[2] In order to obtain reproducibly strong SERS signals, both lithographic and non-lithographic approaches are intensively investigated to produce large-area nanopatterned SERS-active substrates displaying periodically decorated arrays of nanostructures. These methods can provide a controllable periodicity of the plasmonic nanostructures as well as tune the hot-spot density and geometry which are known to influence the electromagnetic enhancement, the major contributor to the SERS signal intensities. Also the control over the structure and the periodicity results in minimum sample-to-sample variation ensuring reproducibility. [3] Herein, we studied a non-lithographic method for fabricating periodically decorated nanoparticle arrays by utilizing the barrier sides of the anodic aluminum oxide (AAO) membranes. These membranes are a class of special biomaterials that are produced from high purity aluminum via two step anodization. The production of the substrates are easy and highly controllable and compared to lithography it is cost-effective. The obtained barrier side of AAO membranes which are periodically nanobump-decorated (NBDS) are further treated with wet etching to create periodic arrays of nanocraters. After coating with an optimized thickness of Au, the nanocrater decorated surfaces (NCDS) displayed intensified SERS signals compared with the NBDS counterparts by using two different model dyes, Methylene Blue and Congo Red. This result was also confirmed with computer simulation studies and it was related to the increased surface roughness for the NCDS substrates. The fabricated Au@NCDS nanoplatforms were stable for extended periods and allowed enhanced (2.3x105 enhancement factor) and reproducible SERS signals with relative standard deviation values ~ 10 % from independently prepared samples and LOD levels down to 10-7 M for Methylene Blue. Our current studies are focused on the potential use of these SERS substrates for sensing biomarker molecules including myoglobin and troponin-T.
[1]Choi, Dukhyun, et al. "Self Organized Hexagonal Nanopore SERS Array." Small 6.16 (2010): 1741-1744.
[2]Cialla, Dana, et al. "Surface-enhanced Raman spectroscopy (SERS): progress and trends." Analytical and bioanalytical chemistry 403.1 (2012): 27-54.
[3]Félidj, N., et al. "Controlling the optical response of regular arrays of gold particles for surface-enhanced Raman scattering." Physical Review B 65.7 (2002): 075419.
10:30 AM - NM07.14.05/NM06.13.05
Multiplexed Surface-Enhanced Raman Immunoimaging In Vivo with Gold Nanoantennas
Yu-Chuan Ou 1 , Joseph Webb 1 , Eden Paul 1 , Christine O'Brien 2 , Isaac Pence 2 , Danielle Cole 1 , Shih-Hao Ou 3 , Maryse Lapierre-Landry 4 , Ethan Lippmann 1 2 , Anita Mahadevan-Jansen 2 , Rizia Bardhan 1
1 Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, United States, 2 Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States, 3 Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States, 4 , Morgridge Institute for Research, Madison, Wisconsin, United States
Show AbstractThe upregulation of immune checkpoint programmed death protein-1 (PD-1) expressed on activated CD8+ T cells, and interaction of PD-1 with its ligand, PD-L1, strongly contributes to an immunosuppressive tumor microenvironment. Blockades of PD-L1 pathway with therapeutic antibodies have shown long-term survival in many cancer patients and several clinical trials are currently ongoing. However, <30% of patients respond to PD-L1 blockade, in part due to inaccurate identification of PD-L1 expression in tumors incurring high costs of immunotherapy and toxicities in patients. Therefore, an unmet clinical need exists for high resolution noninvasive detection techniques. Surface-enhanced Raman microscopy (SERS) imaging mediated by gold nanostructures has gained tremendous interest as a pre-clinical noninvasive diagnostic tool due to the high spatial resolution delineating tumor margin from healthy tissue, multiplexed biomarker detection enabled by the narrow linewidths of Raman footprint, portability, low-cost, and rapid analysis. In this work, we demonstrate the use of gold nanoantennas conjugated with Raman tags for multiplexed SERS imaging enabling the simultaneous diagnosis of PD-L1 and epidermal growth factor receptor (EGFR) in a breast cancer model in vivo. Nanoantennas conjugated with anti-PDL1 antibodies/DTNB Raman molecule, and nanoantennas conjugated with anti-EGFR antibodies/pMBA Raman molecules were concurrently introduced in MDA-MB-231 breast cancer tumors, which are known to overexpress EGFR and PD-L1. Longitudinal Raman analysis demonstrated maximum accumulation of nanoantennas occur 6h post IV delivery when a strong increase in SERS signal for both Raman tag was observed. Raman signal decreased by 30% when both targeted receptors were pre-blocked with antibody (IP), indicating the ability of our platform to distinguish tumors with high and low PD-L1/EGFR expression. Ex-vivo Raman spatial maps correlated well with histology and showed nanoantennas primarily accumulate in the tumor vasculature. The gold content in organs was quantified with inductively coupled plasma mass spectrometry (ICP-MS) to evaluate their pharmacokinetics and uptake in tumor relative to other tissues. ICP-MS analysis showed nanoantennas accumulation in tumors as well as the reticuloendothelial system and substantial clearance within 72 h. This work shows gold nanoantenna mediated SERS imaging provides a quantitative measure of PD-L1 to allow predictive and personalized immunotherapies with minimal toxicities.
10:45 AM - NM07.14.06/NM06.13.06
STED Nanoscopy Assisted by Small Metal Nanoparticles—New Advances
Yonatan Sivan 1 , Nicolai Urban 2 , Matthew Foreman 3 , Stefan Hell 2
1 , Ben-Gurion University, Beer-Sheva Israel, 2 , Max Planck Institute for biological Chemistry, Gottingen Germany, 3 , Imperial College London, London United Kingdom
Show AbstractThe diffraction limit on optical resolution was broken in the early 2000’s in the context of fluorescence microscopy, eventually resulting in the awarding of the Nobel Prize of 2014. The most prominent super-resolution technique is probably stimulated-emission-depletion (STED) nanoscopy, which offers both superb resolution as well as fast acquisition times. To achieve the highest resolution, STED nanoscopes use high laser powers, often requiring expensive laser sources, leading to strong photobleaching.
Recently, we showed that metal nanoparticles can be used to improve the performance of STED nanoscopes with a potential resolution improvement by more than an order of magnitude, or equivalently, depletion intensity reductions by more than 2 orders of magnitude; these come along with a strong photostabilization (i.e. reduction of photobleaching) due to the shortened fluorophore lifetime, which reduces the absolute number of bleaching events.
The first proof-of-concept of this approach, referred to as nanoparticle assisted STED (NP-STED) nanoscopy, was performed with 150nm gold shells, and demonstrated only moderate super-resolution levels. It was also performed in an oil environment.
Here we report the use 20nm gold spheres coated with fluorescent silica in aqueous environment, and a much shorter STED wavelength, of 595nm. First, we demonstrate deep super-resolution with the hybrid nanoparticles, down to ~75nm, at 2 times lower intensities compared with a standard STED. No boiling of the aqueous environment is observed within this range, indicating the applicability to imaging of biological media. The absence of damage indicates that there is no limit on resoltion beside particle size, in sharp contrast to all previously suggested metal particle based imaging schemes.
Second, we demonstrate up to a 3-fold reduction of the bleaching rate in both confocal and STED modes, thus, providing the first confirmation of the second part of the NP-STED theory.
Miniaturization of the NP-STED label and optimization of fluorophore location can enable far better performance. This approach is especially suitable for parallel STED systems where the lack of power is a limiting factor in enabling the scan speed increase. Our hybrid nanoparticles can also enable additional imaging capabilities, e.g. photothermal imaging, nonlinearity-based super-resolution imaging, and most importantly, correlated light-electron imaging, currently highly desired within the microscopy community. Our particles can also enable combination of STED with the multitude of procedures that rely on insertion of plasmonic nanoparticles to cells, including photothermal therapy, membrane perforation, gene therapy treatments, neuron manipulations, drug delivery, as well as Biodiagnostics based on spherical nucleic acids, which are similar to the NPs we used, all of which could benefit from the substantial improvement of the imaging resolution offered by NP-STED.
11:00 AM - NM07.14.07/NM06.13.07
Overcoming the Diffraction Limit—Visualizing Absorption at the Nanometer Scale
Lea Nienhaus 1 2 , Sarah Wieghold 1 2 3 , Joseph Lyding 2 , Ueli Heiz 3 , Friedrich Esch 3 , Martin Gruebele 2
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 , University of Illinois at Urbana-Champaign, Urbana-Champaign, Illinois, United States, 3 , Technical University of Munich, Munich Germany
Show AbstractThe understanding of light induced processes is a key challenge to tailor the optical and electronic properties of materials for their applications in chemical conversion, light harvesting and light emission. Here, nanomaterials are prominent candidates to study the light-material interaction on a single-molecule level, however, due to their size, they are prone to defects, which can be beneficial in applications such as catalysis, however can be detrimental to their function in optoelectronic devices.
Here, we present a technique based on single molecule optical absorption spectroscopy detected by scanning tunneling microscopy (SMA-STM) to image the excited carrier density in various nanomaterials. This technique enables to image the change in the local density of states (LDOS) under modulated illumination with nanometer spatial resolution either via direct absorption in semiconducting materials or indirect absorption in metals.
For direct absorption in semiconducting materials, we are able to correlate the electronic excitation signal of single quantum dots to different angular momentum states based on the sample bias. Excitation of adjacent quantum dot pairs reveals orbital alignment which is indicative of electronic coupling between neighboring quantum dots. [1] In addition, the optical properties of chiral junctions in carbon nanotubes are investigated. Their optoelectronic tunability gives them potential to function as optically or electrically controllable switches. [2]
For indirect absorption in metals however, the excitation results in a plasmon, a collective oscillation of the excited electrons. For future applications in plasmon-induced catalysis, we are investigating the photoactivation of Pt clusters via plasmonic excitation of the support and subsequential electron transfer to the cluster.
The presented results show a novel approach to visualize absorption at the nanoscale and allow a better understanding of light-material interaction at the single molecule level.
[1] Nienhaus et al. J. Am. Chem. Soc. 2015, 137, 14743−14750
[2] Nienhaus et al. ACS Nano 2015, 9 (11), pp 10563–10570
11:15 AM - NM07.14.08/NM06.13.08
Metal Hybrid Co-Based Nanorods for Biosensing, Hyperthermia and Catalytic Properties
Marta Estrader 1 , Nicolas Mille 1 , Julian Carrey 1 , Katerina Soulantika 1 , Bruno Chaudret 1
1 , Laboratoire de Physique et Chimie des Nano-objets (LPCNO), Toulouse France
Show AbstractMultifunctional nanostructures are appealing materials since they combine on a single nano-object different physical and/or chemical properties. Concretely, nanostructured hybrids comprising a magnetic component can be potentially applied in both day to day and high tech applications such as magnetic recording, biotechnology (biosensors, hyperthermia) and catalysis (recoverable catalysts, nanoheaters). In this work we have used, hard-ferromagnetic Co-based nanorods (NRs) as seeds to grow on them Au, Pt, Fe and Ni. Depending on the metal grown on Co, we can modulate the already existing properties, or add new properties not present in the initial Co seed. Thus, the same initial nano-objects can be transformed at will in order to satisfy completely different specifications associated to different applications.
For instance, a mixed shell of Sn, Pt and Au deposited on Co nanorods, prevents Co NRs from oxidation allowing using the Co nanorods in aqueous environment.1 In parallel, Co-Au NRs with a continuous and thick Au shell have been, theoretically, demonstrated as excellent candidates to overcome the nanomolar range detection limit for biosensing applications.2
The interaction of Co with another magnetic metal modifies the hard magnetic character of pure Co nanorods in order to obtain hybrids that can act as magnetically activated nanoheaters and/or nanocatalysts. In this respect, Co-Fe NRs are envisaged to act as nanoheaters in the high temperature catalytic Fischer Tropsch synthesis thanks to the high specific absorption rate values expected as a result of the interaction between the two magnetic metals due to the high saturation magnetization and soft character of Fe and the high Curie temperature of the Co.3 In this line, Co-Ni NRs may even catalyze the methane reforming process where Ni is known to be an excellent catalyst.4 We have developed a synthesis strategy in order to either fully cover the Co NR surface with the second material or mostly only the tips. The growth of a homogeneous shell has been achieved by using an organometallic Sn precursor which it is inferred to reduce the interfacial energy between the two phases.1
1Lentijo-Mozo, S. et al. ACS Nano, 2015, 9, 2792.
2Schrittwieser, S. et al. ACS Nano, 2012, 6, 791.
3Meffre, A. et al. Nano Lett. 2015, 15, 3241.
4Zhao, Z. et al. RSC Adv. 2016, 6, 49487.
11:30 AM - NM07.14.09/NM06.13.09
Tunable Nanoparticles for Light-Triggered Drug Release
Irene Andreu 1 2 , Taeeun Chung 1 , Iris Guo 1 , Matthew Bilton 1 , Byron Gates 1
1 , Simon Fraser University, Burnaby, British Columbia, Canada, 2 , BC Cancer Agency, Vancouver, British Columbia, Canada
Show AbstractEngineered nanomaterials are attractive for cancer treatment due to their small dimensions and the tunability of their properties. A diverse range of engineered nanomaterials has been demonstrated in the literature with tunable shapes, sizes, and compositions aimed at controlling the triggered release of small molecules. One of the strategies has been to utilize the strong light absorption from the localized surface plasmon resonance properties of noble metal nanoparticles. The excitation of the plasmon band can induce heating of the nanoparticles (photothermal effect) to trigger release of drug molecules bonded or in proximity to these nanostructures. The literature reports a range of efficiencies for these photothermal processes. The light-to-heat conversion process is dependent on the overlap of the plasmon band with the incident light, which is tightly related to the shape and surface stabilization of these nanomaterials. Controlled and reproducible synthesis of noble metal nanoparticles is key for the success of the use of the photothermal effect for anticancer drug release. Less noble metal nanoparticles could be used if their photothermal efficiency was sufficiently high, which would reduce the cost and possible side effects of this novel nanotherapeutic approach.
One goal of our studies is to demonstrate methods for fine tuning the plasmon properties of the nanomaterials to improve their photothermal response and, ultimately, their efficiency towards light activated molecular release. Our systematic studies have shown the ability to tune the size of gold nanorods from <30 nm to ~50 nm in length, with longitudinal localized surface plasmon resonance absorbance peak spanning between 600 to 1100 nm. We are also experimentally investigating the mechanism(s) involved in the photothermal response of these materials and their morphological transformations during irradiation with the goal of understanding the potential impacts on drug release and potential use as a platform for therapeutic release. These results could guide the design of engineered nanomaterials with an increased efficiency and stability towards use in light activated and controlled release of therapeutic payloads.
11:45 AM - NM07.14.10/NM06.13.10
Synthesis of Fluorescent CuInS2/ZnS Quantum Dots—Porphyrin Conjugates for Photodynamic Therapy
Ncediwe Tsolekile 1 2 , Parani Sundararajan 1 2 , Mangaka Matoetoe 3 , Sandile Songca 4 , Samuel Oluwatobi Oluwafemi 1 2
1 , University of Johannesburg, Doornfontein South Africa, 2 Centre for Nanomaterials Science Research, University of Johannesburg, Johannesburg South Africa, 3 Department of Chemistry, Cape Peninsula University of Technology, Capetown, Western Cape, South Africa, 4 Chemistry, University of Zululand, Kwadlangezwa, Kwazulu-Natal, South Africa
Show AbstractTernary quantum dots (QDs) such as CuInS2, (CIS) have been extensively investigated for diverse applications such as solar cells, and bioimaging applications due to their unique optical and electronic properties which are related to their composition and crystal structure, tunable bandgap from ultraviolet (UV) to near infrared (NIR) region, biocompatibility etc. These quantum dots have become attractive due to their lower toxicity compared to conventional binary Cd-based QDs. However, these QDs have been majorly synthesized in organic medium which is not ecofriendly. Furthermore, unlike the conventional Cd-based QDs, they usually exhibit blue-shift after passivation. In addressing this problem, we herein report large scale aqueous green synthesis of CIS/ZnS core/shell QDs. The synthesis was performed in a household pressure cooker at 95 oC with water as solvent. Glutathione and sodium citrate were used as dual stabilizing agents to counter the different reactivity’s of the cation precursors. Glutathione furthermore acted as a reducing agent for Cu and to increase bio-compatibility of the QDs. CIS core QDs emitted in the orange region (538 nm) and after the formation of the shell emitted in the red region (619 nm). The red-shift observed with ZnS shell addressed the much-reported blue-shift problem after the shell formation. Transmission electron microscopy (TEM) analysis of the CIS/ZnS QDs showed that, the as-synthesised material are small, mono-dispersed and spherical in shape with average particle diameter of 3.5 nm while FTIR analysis confirmed the glutathione capping. Conjugation of the QDs to porphyrin increased the solubility of the porphyrin as well as its optical properties. This makes the conjugate a viable material for fabrication of solar cell and for photodynamic therapy application.