Symposium Organizers
Piotr Grodzinski National Cancer Institute
Scott Manalis Massachusetts Institute of Technology
Sonke Svenson Cerulean Pharma Inc.
Xing-Jie Liang National Center for Nanoscience and Technology of China
Wenbin Lin University of North Carolina-Chapel Hill
JJ1: Detection of Biomarkers and Biological Response
Session Chairs
Monday PM, November 28, 2011
Room 203 (Hynes)
10:00 AM - **JJ1.1
Nanotheranostics for Cancer: Targeted Nanoparticles for Tumor Imaging, Image-Guided Drug Delivery and Light Induced Therapy.
Paras Prasad 1 2 , Tymish Ohulchanskyy 1
1 Institute for Lasers, Photonics and Biophotonics, State University of New York at Buffalo, Buffalo, New York, United States, 2 Chemistry, State University of New York at Buffalo, Buffalo, New York, United States
Show AbstractFor cancer therapy, nanoparticles provide a platform combining multimodal diagnostics (e.g., medical imaging) with multipronged therapy. The talk will provide examples of our efforts in designing multifunctional nanoparticles of ceramic, polymeric, semiconductor and metallic composition, for applications in diagnostics and therapy of cancer. The biocompatible or biodegradable nanomaterials, such as polymeric nanomicelles and nanoparticles, heavy metal-free quantum dots (silicon nanocrystals), fluoride nanocrystals, magnetic (iron oxide) and plasmonic (gold) nanoparticles, and their combination, will be discussed. The composition, porosity and surface properties of the nanoparticles have been tailored to enable targeted and image-guided drug delivery and/or light-activated therapy. Multimodal nanoplatforms containing multiple imaging and sensing probes have been developed, which will enable the integration of imaging/sensing at the cellular, tissue and whole-body level using a single formulation. Our recent results on nanoparticle mediated gene-silencing for overcoming the inherent radio/chemo-resistance of cancer cells will be also presented. Incorporation of both diagnostic (multimodal imaging) and therapeutic payload within a single nanoplatform have provided the ability for triggering on-demand therapy, along with monitoring the efficacy of treatment in real-time. This talk will conclude with a discussion of examples of new challenges and opportunities in these fields. 1.P.N.Prasad, “Introduction to Biophotonics”, Wiley Interscience, New York (2003).2.P. N. Prasad “Nanophotonics”, John Wiley & Sons, New York (2004).3.P. N. Prasad “Inroduction to Nanomedicine and Nanobioengineering”, to be published by John Wiley & Sons.
10:30 AM - JJ1.2
Novel Multifunctional Nanocarriers Capable of In Vivo Rapidly Controlled Drug Release for MR Imaging and Targeted Epilepsy Therapy.
Hsin-Yang Huang 1
1 Department of Materials Sciences and Engineering, National Chiao Tung University, Hsin Chu, TAIWAN, Taiwan
Show AbstractThermosensitive nanocarrier were synthesized by incorporation of iron oxide nanoparticles (NPs) and hydrophobic drug molecules into the negative thermosensitive matrix composed of PEO-PPO-PEO (F127) and the H-bond provider of PVA via mini-emulsion process. The developed novel drug-delivery vectors capable of achieving remotely triggered burst drug release in vivo in a few seconds, which is very important for chronic disease needed to be treated in a short time such as epilepsy. Under exposure to high frequency magnetic field (HFMF), heat was generated from the iron oxide NPs in the carriers, leading to an immediate deformation of hydrogen bonds as well as rapid collapse of the nanostructure, in which a large amount of imbibed drug can be rapidly released out in the real time. However, in the absence of the HFMF, the nanocarriers displayed a relatively stable morphology without any leakage and showed low drug release rate, indicating the drug molecules remained well in the matrix. In this in vivo study, an anti-epilepsy drug, ESM (ethosuximide), was encapsulated in this magnetically-thermal sensitive nanocarrier. While subjecting to HFMF in few seconds, it was found that the ESM was burst released from the carrier in the Long-Evans rat model, which has demonstrated a significant reduction in spike-wave discharge, indicating the potential application of the drug-carrying magnetic carriers as the building blocks that ensure a rapid and precise response to magnetic stimulus. The nanocarriers are also shown to be good candidates for magnetic resonance imaging (MRI) contrast agents as demonstrated by the high r2/r1 ratio (438) with long-term stability under magnetic field. Together with well-regulated controlled release design and the MRI, the nanocarrier not only shows clear MR image of acute epilepsy nodus, but also latent one. Based on this preliminary study, the investigation of multifunctional nanocarriers for in vivo controlled drug release combining with imaging and targeted therapy is now in progress in our group and will be reported in this meeting.
10:45 AM - JJ1.3
``AND'' Logic T1-T2 Nanoparticles for Fault-Free MR Imaging.
Jin-sil Choi 1 , Tae-hyun Shin 1 , Dongwon Yoo 1 , Ho-Taek Song 2 , Eung Yeop Kim 2 , Jinwoo Cheon 1
1 Dept. of Chemistry, Yonsei University, Seoul Korea (the Republic of), 2 Department of Radiology , College of Medicine, Yonsei University, Seoul Korea (the Republic of)
Show AbstractAccuracy in the diagnostics is one of the critical issues in biomedical sciences because it affects on the decision of the medical treatment processes and determines the survival rate of the patient. Devising dual imaging tools in single imaging system would be an attractive way to pursue. In particular, for MRI, to enhance imaging accuracy, two different imaging modes with specific contrast agents are being used; one is T1 type which generates “positive” signal enhancements and the other one of T2 type which gives “negative” signal enhancements. When present together, these contrast agents can potentially provide highly sensitive and valuable complementary diagnostic information in real time by simply switching the scanning mode in MRI. However, the realization of such a contrast agent with well-defined T1 and T2 capabilities has been difficult because T1 signal is strongly quenched by T2 agent when they are combined together. Here, we demonstrate the design and systematic construction of an innovative T1-T2 dual modal nanoparticle contrast agent which exhibits simultaneously strong T1 and T2 signal enhancements. Developed nanoparticles can have “AND” logic where imaging area with both T1 and T2 signals satisfy the “AND” and self-confirms the validity of the results from each imaging mode. We also show that a variety of new type of dual mode contrast agents can be obtained by the combinations of different T1 and T2 nanomaterials.
11:00 AM - JJ1.4
Quantum-Dot-Decorated Enzyme Nanocapsules for Cancer Imaging and Therapeutics.
Juanjuan Du 1 , Ming Yan 1 , Titiana Segura 1 , Yi Tang 1 , Yunfeng Lu 1
1 Department of Chemical and Biomolecular Engineering, UCLA, Los Angeles, California, United States
Show AbstractCancer is a leading cause of death worldwide. Developing safe and efficient cancer therapy has long been pursued by scientists and doctors. In this context, a combination of therapeutics with imaging, which potentially eliminates the unnecessary treatments and provides means to monitor treatments, could result in significant increased drug efficacy and safety. Our work presented here, based on a quantum-dot-decorated enzyme nanocapsule (QDEN) structure, integrates bioluminescence imaging with enzyme-targeted prodrug therapy, providing a prototype for combined cancer diagnostics and therapeutics. The fabrication of QDEN is simple and biomolecule-compatible. Using aqueous in-situ polymerization on bioluminescent enzyme horseradish peroxidase (HRP) anchored with polymerizable vinyl groups, we obtained nano-sized core-shell nanocapsules with enzyme as the core and crosslinked thin polymer net as the shell. HRP in the core of QDENs, together with indole-3-acetic acid, is also proposed as a prodrug cancer therapy agent. The resulted nanocapusles possess greatly enhanced stability, retained bioactivity, and readily engineered surface. In particular, by incorporating polymerizable amines in the polymerization, we endowed the nanocapsules with efficient cell-transduction and sufficient conjugation sites for follow-up modification. Following in-situ polymerization, decorating the polymer shell with fluorescent quantum dots allowed us to access continuous tunable wavelength, which extends the application of such bioluminescent nanocapsules, especially in deep tissue. In addition, the unique core-shell structure and adequate conjugation sites on surface enabled us to maximize the BRET efficiency by adjusting the QD/enzyme conjugation ratio. Additional functionalization of surface with targeting modality features the QDENs with cancer targeting capabilities, enabling the potential applications of QDENs as cancer imaging and therapeutic agents.
11:30 AM - **JJ1.5
Magnetic Nanoparticles for Theranostics and Cell Actuations.
Jinwoo Cheon 1
1 , Yonsei University, Seoul Korea (the Republic of)
Show AbstractOne of the important trends of next-generation nanomedicine is theranostics that is defined by the combination of therapeutics and diagnostics on a single platform. Magnetic nanoparticles are among one of the most essential platforms for targeted imaging, therapy, and simultaneous monitoring of therapeutic efficacy. In this talk, I will discuss magnetic nanoparticles as a core platform material for theranostics and add a variety of functionalities such as drug, targeting moiety, and gene to enhance their performance. Their unique utilization in highly accurate dual-modal MR imaging, therapeutic hyperthermia of cancer cells, controlled drug release, and molecular level cell signaling and cell fate control will be discussed.
12:00 PM - JJ1.6
Magnetic Nanoparticles as MRI Contrast Agents and for Selective Targeting of Cells.
Wolfgang Tremel 1 , Thomas Schladt 1 , Bahar Nakhjavan 1 , Kerstin Koll 1 , Heiko Bauer 1 , Oskar Koehler 1 , Isabell Schick 1 , Anna Schilmann 1 , Muhammad Tahir 1 , Filipe Natalio 1 , Peter Bluemler 2 , Kerstin Muennemann 3
1 Institut für Anorganische Chemie, Johannes Gutenberg-Universität, Mainz Germany, 2 Institut für Physik, Johannes Gutenberg-Universität, Mainz Germany, 3 , Max Planck-Institut für Polymerforschung, Mainz Germany
Show AbstractOne of the goals for biomedical applications of nanoparticles is their functionalization to impart precise biological functions. Nanomaterials can be loaded with low molecular drugs or large molecules like ribonucleic acids (RNA) which are inherently difficult to deliver due to their size and polarity. Nanoparticles are attractive probe candidates because of their (i) size and surface-to-volume ratio, (ii) tunable physical properties directly related to size, composition, and shape, (iii) unusual target binding properties, and (iv) structural robustness. We have developed biocompatible materials by surface functionalization of MnO nanoparticles using polymers or porous silica coatings that simultaneously (i) carry ligands (poly(I:C), CpG, etc.) and (ii) large target molecules (e.g. antibodies for target detection), (iii) small molecules (e.g. drugs) through non-specific binding, and (iv) fluorophors for optical detection. (v) In addition, the nanoparticles can be traced using magnetic resonance imaging (MRI) by virtue of the magnetic properties. Cytotoxicity was evaluated by an electric cell-substrate impedance sensing (ECIS) micromotion assay. The ssDNA and CpG coupled nanoparticles were used to target Toll-like receptors (TLR3 and TLR9) receptors inside the cells and to activate the classical TLR cascade. The multimodal nanoparticles allow optical as well as MRI imaging of cellular trafficking. For in vivo MRI imaging, the water-dispersible functionalized MnO nanoparticles were injected into the tail vene of nude mice. The MnO nanoparticle contrast-enhanced T1-weighted MRI showed contrast-enhanced regions following accumulation of MnO nanoparticles in the tumor.In addition, Janus-type (M-1)@(M-2 oxide) (M-1: Au, Ag, Cu, Pt, Rh, Co and Fe/Pt); M-2: MnO, Fe3O4) were synthesized by thermal decomposition of metal salts in the presence of metal colloids. In particular, the surface chemistry of both domains can be functionalized independently, where tumor cells were addressed by conjugated antibodies, CpG ligands were attached for immunotherapy and an effective killing of the cells could be achieved under illumination with NIR light. Depending on the chemical anisotropy Janus particles can form superamphiphiles or giant dipoles producing particles with unprecedented properties. The new properties are of considerable interest due to their substantial membrane activity.
12:15 PM - JJ1.7
Modulating the Luminescence of Upconverting Nanoparticles Using Dithienylethene Photoswitches for Biolabeling Applications.
John-Christopher Boyer 1 , Carl-Johan Carling 1 , Neil Branda 1
1 Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada
Show AbstractPhotoactivatable fluorophores are powerful tools for increasing the temporal and special resolution in bioimaging. Upconverting nanoparticles (UCNPs) possess several properties that make them ideal for use as biolabels including increased photostability, absence of blinking, and low excitation densities but have yet to be designed for microscopic photoactivation. At the same time the use of dithienylethene (DTE) photoswitches to achieve control of physical and chemical molecular properties has been well documented in recent years. Through the combination of upconverting nanoparticles (UCNPs) and DTE photoswitches we are able to create photomodulated upconverting biolabels. Using the absorption of the DTE photoswitch we are able to selectively quench the luminescence of the UCNP. By modulation the switch with UV and visible light we are able to selectively turn off and on the upconversion luminescence respectively. Our system has an advantage over caged fluorophores as the luminescence of our UCNPs can be cycled through the on and off state multiple times.
12:30 PM - JJ1.8
Incorporation of Quantum-Dots with Mesoporous Silica Nanoparticles for Intracellular Targeting and In Vivo Images.
Po-Jung Chen 1 , Shang-Hsiu Hu 2 , San-Yuan Chen 3 , Dean-Mo Liu 4
1 , National Chiao Tung University, Hsinchu Taiwan, 2 , National Chiao Tung University, Hsinchu Taiwan, 3 , National Chiao Tung University, Hsinchu Taiwan, 4 , National Chiao Tung University, Hsinchu Taiwan
Show Abstract In this study, a nanosystem is constructed using facile technology by embedding different-sized hydrophobic quantum dots (QDs) into mesoporous silica nanoparticles which pore size distribution is 5 nm in radius, and lipid-PEG2000-COOH coated to be encoded with cRGD targeting peptide through biotin-streptavidin bridges. Their novel optical properties render these highly luminescent QDs ideal fluorophores for wavelength-and-intensity multiplexing, and through hydrophobic interaction between the hydrocarbon and TOPO molecules to stabilized QDs in the porous nanobeads. In the solvents (eg., water, ethanol and butanol), none of QDs can be leaked from the porous nanobeads. Furthermore, the QDs tagged mesoporous silica nanoparticles show clearly images sensing not only in vitro but also in vivo of the nude mice. The cRGD-encode lipid coated QDs tagged nanobeads (cRGD-encoded LQNPs) show significantly increased αvβ3-expressing cell targeting in MCF-7 breast cancer cells over than αvβ3-low expressing HeLa cervix cancer cells, which is confirmed by confocal laser scanning microscopy and flow cytometry. In addition, the QNPs also demonstrated fairly high cell viability comparing to free 3-mercaptopropionic acid (MPA)-functionalized QDs. The cRGD-encoded LQNPs introduced here represent a new platform for nanoparticulate multimodality αvβ3-specific response bioimaging agents.
JJ2: Imaging and In-vivo Detection Using Nanoparticles
Session Chairs
Monday PM, November 28, 2011
Room 203 (Hynes)
2:30 PM - **JJ2.1
Multiplex Wash-Free Magneto-Nanosensors for Cancer Diagnostics and Drug Development.
Shan Wang 1
1 Materials Science and Engineering, Stanford University, Stanford, California, United States
Show AbstractReproducible and multiplex protein assays are greatly desired by cancer biologists as well as clinical oncologists to rapidly follow numerous proteins in clinical samples. This will allow physicians to determine the efficacy of relevant chemotherapy in real time or to detect cancer early, e.g., stage 1 ovarian cancer, so that cancer survival rates can be improved greatly. We have now successfully applied magneto-nano biochips based on giant magnetoresistance (GMR) spin valve sensor arrays and magnetic nanoparticle labels (nanotags) to the detection of biological events in the form of multiplex protein assays (4-to 64-plex) with great speed (30 min. – 2 hours), sensitivity (1 picogram/milliliter concentration levels or below), selectivity, and economy [1-3].More recently, we achieved the first demonstration of a nanolabel-based technology capable of rapidly isolating cross-reactive antibody binding events in a highly multiplex manner. By combining magnetic nanotechnology with immunology, we have devised an easy to use and rapid auto-assembly assay which is ideal for high-density screens of aberrant protein binding events [4]. Such a technology has the potential to revolutionize the current practices in the proteomics and drug development community by providing researchers with the tools to rapidly investigate both on and off-target protein binding events. Furthermore, this technology is more sensitive and specific than label-free technologies (e.g., Surface Plasmon Resonance (SPR) based approaches such as Biacore), can be scaled up more readily, and consumes far less valuable reagents [5].References: [1] Gaster RS, Hall DA, et al., Nature Medicine, 15, 1327-1332, 2009.[2] Osterfeld SJ, Yu H, et al., PNAS, 105, 20637-20640, 2008.[3] Hall DA, Gaster RS, et al., Biosensors and Bioelectron., 25, 2051-2057, 2010.[4] Gaster RS, Hall DA, Wang SX, Nano Letters, published online, DOI: 10.1021/nl1026056.[5] Gaster RS et al., Nature Nanotechnology, 6, 314-320, 2011.
3:00 PM - JJ2.2
Quantitative Analysis of Multiple Urinary Biomarkers of Carcinoid Tumors through Gold-Nanoparticle-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry.
Tsung-Rong Kuo 1 4 , Jinn-Shiun Chen 2 , Yu-Chen Chi 1 , Chia-Yi Tsai 3 , Cho-Chun Hu 3 , Chia-Chun Chen 1 4
1 Chemistry, Natl Taiwan Normal University, Taipei Taiwan, 4 Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei Taiwan, 2 Division of Colorectal Surgery, Chang Gung University, Taoyuan Taiwan, 3 Natural Science Education, National Taitung University, Taitung Taiwan
Show AbstractIn this work, a simple technique for quantitative analysis of four urinary biomarkers, tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine and 5-hydroxyindole acetic acid of carcinoid tumors is developed using gold nanoparticles as the assisted matrix in surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI-TOF MS). The optimal SALDI conditions for the efficient ionization of those biomarkers are systematically explored by the adjustments of the concentrations of gold nanoparticles and internal standards. The calibration curves of the biomarker concentrations are determined using SALDI-TOF MS and the high linearity is obtained in all samples. For future clinical testing, multiplexed detection of those biomarkers in the urine samples of healthy males is performed. The successful quantitative detections of those biomarkers indicate that our technique provides a rapid and accurate platform for clinical screening of carcinoid tumors.
3:15 PM - JJ2.3
High-Performance Electrochemical Sensing of Cancerous Protease (Legumain) Using Nanoelectrode Arrays.
Lateef Uddin Syed 1 , Luxi Zhang 1 , Allan Prior 1 , Jianwei Liu 1 , Duy Hua 1 , Jun Li 1
1 Chemistry, Kansas State University, Manhattan, Kansas, United States
Show AbstractGlobally, thousands of lives are lost every day from various types of cancers. The best way of preventing these deaths is early diagnosis and effective treatment. It is well known that overexpression of certain enzymes such as kinases, phosphatase, and proteases causes cancers. Legumain (also known as asparaginyl endopeptidase) is a lysosomal cysteine protease whose activity is found in several tissues. Legumain is found highly expressed in a majority of tumors including carcinomas of the breast, colon, and prostate, and in central nervous system neoplasms. However, overexpression is not found in normal cells. Legumain is present intracellularly in endosome/lysosome systems and extracellularly in tumor microenvironment, consequently making it a potential cancer biomarker. It has also been reported that legumain specifically cleaves asparaginyl carbonyl bond. Nanostructured carbon materials have attracted extensive attention for various electroanalytical applications, particularly in the form of nanoelectrodes. In the present study, we employed embedded vertically aligned carbon nanofiber (VACNF) nanoelectrode array (NEA), where only the ends of carbon nanofibers (CNFs) are exposed at the surface of the insulating SiO2 matrix. The exposed CNF tips were functionalized with an electroactive ferrocene (Fc)-linked tetrapeptide (Ala-Ala-Asn-Leu-Fc). The asparagine site (C-terminus) of the tetrapeptide is cleaved by legumain, which results in the release of Fc moieties from the electrode to the bulk solution, leading to a drastic decrease in the electrochemical signal. Towards achieving this goal, as a first step to understand the electron transfer phenomenon at the CNFs, the exposed CNF tips were functionalized with Fc moieties and a careful electrochemical investigation of electron transfer rate (ETR) with direct current (DC) and alternating current (AC) voltammetric techniques was carried out. Our results show striking difference in ETR between DC and AC voltammetric measurements, revealing an anomalous phenomenon of electron transfer at CNF NEAs that is likely defined by the intrinsic properties of CNFs rather than the faradaic process at the electrode surface. We observed 100 times higher ETR by AC voltammetry than by DC voltammetry. The electrochemical properties of the nanoelectrode were found to critically depend on the unique conical graphitic stacking of the CNFs, which facilitates a new capacitive pathway in high-frequency AC voltammetric measurements. This study indicates that selecting an appropriate electrochemical technique can cope with the intrinsic limit of nanoelectrode materials. Particularly, high-frequency AC voltammetry can provide high-performance nano-biosensors and nanoelectronics with CNF NEAs. These findings are being utilized to build an ultrasensitive legumain biosensor for electrochemical monitoring of legumain activity in various cancerous cell lines.
3:30 PM - JJ2.4
Investigating Receptor-Ligand Interactions on Tunable Nanostructured, Biofunctionalized Surfaces under Flow.
Sebastian Kruss 1 2 , Luise Erpenbeck 3 , Michael Schoen 3 , Joachim Spatz 1 2
1 , MPI for Intelligent Systems, Stuttgart Germany, 2 Physical Chemistry, Heidelberg University , Heidelberg Germany, 3 Department of Dermatology, Göttingen University, Heidelberg Germany
Show AbstractThe interaction of cells in the bloodstream with vascular endothelial cells is crucial for many physiological and pathological processes within the organism, inflammation and hematogenous cancer metastasis being the most prominent examples. In the past decades, many approaches have been taken to unravel these complex mechanisms. However, in vivo investigation of single receptor-ligand interactions can be difficult due to the high complexity of these model systems. In vitro models, on the other hand, also have severe limitations as they often do not allow simultaneous control of biophysical parameters such as shear rate, receptor density or clustering. For this reason, our goal was to design a flow chamber system which is based on the “classical” parallel plate flow chamber while allowing a precise modulation of said biophysical parameters. To design surfaces with precisely tunable densities of biomolecules, nanopatterns of 6 nm gold nanoparticles were created by self-assembly of diblock copolymer micelles on glass substrates. The distance between gold nanoparticles can be adjusted, ranging from 25 nm to 250 nm. Furthermore, clustering effects and density gradients can be mimicked. Biomolecules such as different selectins or selectin receptors can then be bound to the gold nanoparticles in a site directed manner. In contrast to conventional protein-adsorption methods on surfaces, this ensures biologically correct presentation of the binding epitopes. The glass substrates can then be integrated into a flow chamber system in which hydrodynamic parameters can be controlled. Interaction of cells of the blood stream such as leukocytes and tumor cells or of beads presenting only a certain kind of ligand can then be surveyed. This novel approach to investigate ligand-receptor interactions allows the determination of important biophysical parameters of said interactions, such as maximum and minimum shear rates needed for receptor interactions, shear and ligand density thresholds as well as life-times of the interaction.
3:45 PM - JJ2.5
Exploring the Impact of Cell Mechanics on Cancer Progression with the Microfluidic Optical Stretcher.
Mareike Zink 1 , Franziska Wetzel 1 , Anatol Fritsch 1 , Steve Pawlizak 1 , Tobias Kiessling 1 , Kenechukwu Nnetu 1 , Lars-Christian Horn 2 , Michael Hoeckel 3 , Josef Kaes 1
1 Soft Matter Physics Division, University of Leipzig, Leipzig Germany, 2 Institute of Pathology, University of Leipzig, Leipzig Germany, 3 Department of Obstetrics and Gynecology, University of Leipzig, Leipzig Germany
Show AbstractBiophysics established a new research area which described the progression of cancer from a materials science perspective. It has been know for a long time that malignant transformation is associated with significant changes in the cellular cytoskeleton. If the cytoskeleton’s alterations are necessary for malignant transformation, they have to trigger biomechanical changes that impact cellular functions. The Microfluidic Optical Stretcher (MOS) is a fully automatic technique to marker and contact-free probe the mechanical properties of cells with a through-put of several hundred cells per hour. Since cytoskeletal properties such as actin concentration are non-linearly correlated with the shear modulus of the cell and changes are amplified up to the power of 7, even small alterations of the cytoskeleton during malignant transformations can be detected from optical deformations. MOS experiments with tumor cell lines clearly show that malignant transformation causes cell softening for small deformations which correlates with an increased rate of proliferation compared to normal cells. Additionally, three clinical studies were carried out to prove the potential of the MOS for cancer diagnosis. First, primary oral squamous carcinoma cells from patients with early dysplasia and malignant tumors were probed with the MOS and compared with the deformability of primary oral cells from healthy donors. Second, breast tumor cells were resected from the women’s body and deformed within the MOS together with primary normal breast epithelial cells. Third, primary cervix carcinoma cells and normal epithelial cells resected from the same morphological compartment of the same women were examined. From all experiment we clearly found that tumor cells are softer compared to normal cells and exhibit a broader distribution of optical deformability. Since cell softening during malignant transformation seems to be a universal behavior of tumor cells, the MOS offers the possibility to detect many different types of tumors without any further knowledge of the molecular details of the cells. Thus, the MOS is a novel and highly promising tool for cancer diagnoses since highly expensive and specific molecular markers that only detect single alteration on the molecular level can be neglected.
4:30 PM - **JJ2.6
Implanted Diagnostic Devices.
Michael Cima 1 2
1 Department of Materials Science & Engineering, Massachusetts Inst. of Technology, Cambridge, Massachusetts, United States, 2 The David H. Koch Institute for Integrative Cancer Research, Massachusetts Inst. of Technology, Cambridge, Massachusetts, United States
Show AbstractImplantable magnetic resonance (MR) readable sensors afford the opportunity to detect various biomarkers in vivo and in real time. These measurements can be made through multiple layers of tissue and in a non-invasive manner. This talk focuses on two such sensors—the first a nanoparticle-based device for detecting cardiac biomarkers, and the second a sensor comprising of an MR-sensitive material for measuring tissue oxygenation.Nanoparticle-based sensors work on the principle that iron oxide nanoparticles clustered around analyte molecules can change the transverse relaxation time c