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SUMMARY:Ultrasensitive Digital Detection of Nanoparticles: Viral Diagnosti
 cs and Multiplexed Protein and Nucleic Acid Assays
DTSTART:20140618T101500
DTSTAMP:20260610T173734Z
UID:f5d995f7e432ff39a220c0040d7b0a47d4797e8acaa4790e335126b1
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. M. Selim Ünlü\, Boston University\, Biomedical Enginee
 ring Department (Boston\, MA\, USA)\nJOINT BIO- and ELECTRICAL ENGINEERING
  SEMINARAbstract:\nDirect monitoring of primary molecular binding interact
 ions without the need for secondary reactants would markedly simplify and 
 expand applications of high-throughput label-free detection methods. We ha
 ve developed the Interferometric Reflectance Imaging Sensor (IRIS) for lab
 el-free\, high throughput\, high sensitivity and dynamic detection of mole
 cular binding on a solid surface.  IRIS has demonstrated protein-protein 
 binding and DNA-protein binding in real time\, label-free\, and in a high-
 throughput format with high sensitivity (~10 pg/mm2) and reproducibility [
 1\,2] as well as label-free measurements of DNA hybridization kinetics [3]
  and viral detection [4].\nSynthetic nanoparticles have made significant i
 mpact across a broad range of technological applications including optical
  nanoantennas\, ultra-sensitive imaging and sensing\, and diagnostics and 
 therapeutics. Natural nanoparticles such as viruses and pollutants are inv
 olved in global health problems. High-throughput characterization of nanop
 articles in terms of their size and shape is crucial for practical applica
 tions of synthetic nanoparticles and highly sensitive pathogen identificat
 ion. Recently\, we have demonstrated IRIS with the ability to detect singl
 e nanoscale particles [5\,6].\nIn single-particle modality of IRIS (SP-IRI
 S)\, the interference of light reflected from the sensor surface is modifi
 ed by the presence of particles producing a distinct signal that reveals t
 he size of the particle. In our approach the dielectric layered structure 
 acts as an optical antenna optimizing the elastic scattering characteristi
 cs of nanoparticles for sensitive detection and analysis. We have successf
 ully detected 35 nm and 50 nm radius particles and H1N1 viruses with accur
 ate size discrimination [5]. We have demonstrated identification of virus 
 particles in complex samples for replication-competent wild-type vesicular
  stomatitis virus (VSV)\, defective VSV\, and Ebola- and Marburg-pseudotyp
 ed VSV. Size discrimination of the imaged nanoparticles (virions) allows d
 ifferentiation between modified viruses having different genome lengths an
 d facilitates a reduction in the counting of non-specifically bound partic
 les to achieve a limit-of-detection (LOD) of 5x103 pfu/mL for the Ebola an
 d Marburg VSV pseudotypes. We have demonstrated the simultaneous detection
  of multiple viruses in serum or whole blood as well as in samples contami
 nated with high levels of bacteria [7]. Single nanoparticle detection with
  IRIS has shown promising  results for protein [8] and DNA arrays with at
 tomolar detection sensitivity.References:\n1.   Ozkumur E.\, J. W. Needh
 am\, D. A. Bergstein\, R. Gonzalez\, M. Cabodi\, J. M. Gershoni\, B. B. Go
 ldberg\, and M. S. Ünlü. "Label-free and Dynamic Detection of Biomolecul
 ar Interactions for High-throughput Microarray Applications." Proceedings 
 of the National Academy of Sciences\, Vol. 105\, No. 23\, Pages: 7988-7992
 \, (2008)\n2. Özkumur E.\, A. Yalç?n\, M. Cretich\, C. A. Lopez\, D. A. 
 Bergstein\, B.  B. Goldberg\, M. Chiari\, and M. S. Ünlü. "Quantificati
 on of DNA and Protein Adsorption by Optical Phase Shift." Biosensors and B
 ioelectronics\, Vol. 25\, No. 1\, 167-172\, (2009)\n3.   E. Ozkumur\, S.
  Ahn\, A. Yalcin\, C. Lopez\, E. Cevik\, R. Irani\, C. DeLisi\, M. Chiari\
 , and M. S. Ünlü\, "Label-free microarray imaging for direct detection o
 f DNA hybridization and single-nucleotide mismatches\," Biosensors and Bio
 electronics\, Vol. 25\, No. 7\, 15\, pp. 1789-1795\, (2010)\n4.   C. Lop
 ez\, G. G. Daaboul\, R. S. Vedula\, E. Ozkumur\, D. A. Bergstein\, T. W. G
 eisbert\, H. Fawcett\, B. B. Goldberg\, J. H. Connor\, and M. S. Ünlü\, 
 "Label-free multiplexed virus detection using spectral reflectance imaging
 \," Biosensors and Bioelectronics\, doi:10.1016/j.bios.2011.01.019\, (2011
 )\n5.   G. G. Daaboul\, A. Yurt\, X. Zhang\, G. M. Hwang\, B. B. Goldber
 g\, and M. S. Ünlü\, "High-Throughput Detection and Sizing of Individual
  Low-Index Nanoparticles and Viruses for Pathogen Identification\," Nano L
 etters\, Vol. 10\, No. 11\, pp. 4727-4731 (2010)\n6. A. Yurt\, G. G. Daabo
 ul\, J. H. Connor\, B. B. Goldberg\, and M. S. Ünlü\, "Single nanopartic
 le detectors for biological applications\," Nanoscale\, Vol. 4\, No. 3\, 2
 012\, pp. 715 – 726\n7. GG Daaboul\, CA Lopez\, J Chinnala\, B Goldberg\
 , JH Connor\, and MS Ünlü\, “Digital Sensing and Sizing of Vesicular S
 tomatitis Virus Pseudotypes in Complex Media: A Model for Ebola and Marbur
 g Detection\,” ACS Nano\, 2014\n8.   M. R. Monroe\, G. G. Daaboul\, A.
  Tuysuzoglu\, C. A. Lopez\, F. F. Little\, and M. S. Ünlü\, "Single Nano
 particle Detection for Multiplexed Protein Diagnostics with Attomolar Sens
 itivity in Serum and Unprocessed Whole Blood\," Analytical Chemistry\, Vol
 . 85\, No. 7\, March/April 2013\, pp. 3698-3706Bio:\nCurrently at Boston U
 niversity\, Biomedical Engineering Department (Boston\, MA\, USA):\nProfes
 sor\, Biomedical Engineering\nProfessor\, Electrical and Computer Engineer
 ing\nAssociate Director\, Center for Nanoscience and Nanobiotechnology\nEd
 ucation:\nM.S. & Ph.D.\, University of Illinois\, Urbana-Champaign\nB.S.\,
  Middle East Technical University\, Ankara\, Turkey
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