Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-28T09:25:46.919Z Has data issue: false hasContentIssue false
  • English
  • Français

Digital Detection of Nanoparticles: Viral Diagnostics and Multiplexed Protein and Nucleic Acid Assays

Published online by Cambridge University Press:  13 January 2015

M. S. Ünlü
M. S. Ünlü*
Affiliation:
Boston University, Department of Electrical and Computer Engineering, Department of Biomedical Engineering and Photonics Center Boston, MA 02215, U.S.A.
Get access

Abstract

Synthetic nanoparticles have made significant impact 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 major concerns for human health. High-throughput characterization of nanoparticles in terms of their size and shape is crucial for practical applications of synthetic nanoparticles and highly sensitive pathogen identification. Recently, we have demonstrated Interferometric Reflectance Imaging Sensor (IRIS) with the ability to detect single nanoscale particles [1,2].

In single-particle modality of IRIS (SP-IRIS), the interference of light reflected from the sensor surface is modified by the presence of particles producing a distinct signal that reveals the size of the particle. In our approach, the dielectric layered structure acts as an optical antenna optimizing the elastic scattering characteristics of nanoparticles for sensitive detection and analysis. We have demonstrated identification of virus articles in complex samples for various viruses in multiplexed format. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of non-specifically bound particles to achieve a limit-of-detection (LOD) of 5x103 pfu/mL for the Ebola and Marburg VSV pseudotypes. We have demonstrated the simultaneous detection of multiple viruses in serum or whole blood as well as in samples contaminated with high levels of bacteria [3]. Single nanoparticle detection with IRIS has shown promising results for protein [4] and DNA arrays with attomolar detection sensitivity.

Keywords

biologicalsensornanoscale
Type
Articles
Information
MRS Online Proceedings Library (OPL) , Volume 1720: Symposium D – Materials and Concepts for Biomedical Sensing , 2014 , mrsf14-1720-d01-01
Copyright
Copyright © Materials Research Society 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Daaboul, G. G., Yurt, A., Zhang, X., Hwang, G. M., Goldberg, B. B., and Ünlü, M. S, “High-Throughput Detection and Sizing of Individual Low-Index Nanoparticles and Viruses for Pathogen Identification,” Nano Letters, Vol. 10, No. 11, pp. 4727–4731, (2010)CrossRefGoogle ScholarPubMed
Yurt, A., Daaboul, G. G., Connor, J. H., Goldberg, B. B., and Ünlü, M. S, “Single nanoparticle detectors for biological applications,” Nanoscale, Vol. 4, No. 3, pp. 715 – 726, (2012)CrossRefGoogle ScholarPubMed
Daaboul, GG, Lopez, CA, Chinnala, J, Goldberg, B, Connor, JH, and Ünlü, MS, “Digital Sensing and Sizing of Vesicular Stomatitis Virus Pseudotypes in Complex Media: A Model for Ebola and Marburg Detection” ACS Nano, DOI: 10.1021/nn501312q, (2014)CrossRefGoogle ScholarPubMed
Monroe, M. R., Daaboul, G. G., Tuysuzoglu, A., Lopez, C. A., Little, F. F., and Ünlü, M. S, “Single Nanoparticle Detection for Multiplexed Protein Diagnostics with Attomolar Sensitivity in Serum and Unprocessed Whole Blood,” Analytical Chemistry, Vol. 85, No. 7, pp. 3698–3706, (2013)CrossRefGoogle ScholarPubMed
van Dijk, M. A., Tchebotareva, A. L., Orrit, M., Lippitz, M., Berciaud, S., Lasne, D., Cognet, L. and Lounis, B., Phys. Chem. Chem. Phys., 8, 3486–3495 (2006)CrossRefGoogle Scholar
Hunt, H. K. and Armani, A. M., Nanoscale, 2, 1544–1559 (2010)CrossRefGoogle Scholar
Biswas, A., Wang, T. and Biris, A. S., Nanoscale, 2, 1560–1572 (2010)CrossRefGoogle Scholar
See for example: G. Airy, Philos. Mag. 2, 20 (1833), and F. Perot and C. Fabry, Astrophys. J. 9, 87(1899).Google Scholar
Brecht, A., Gauglitz, G., Polster, J., “Interferometric immunoassay in a FIA-system: a sensitive and rapid approach in label-free immunosensing,” Biosens. Bioelectron. 8, 387–392. doi:10.1016/0956-5663(93)80078-4 (1993).CrossRefGoogle Scholar
Ozkumur, E., Needham, J., Bergstein, D. A., Gonzalez, R., Cabodi, M., Gershoni, J., Goldberg, B. B., and Ünlü, M. S, “Label-free and dynamic detection of biomolecular interactions for high-throughput microarray applications,” Proceedings of the National Academy of Science, Vol. 105, pp. 7988–7992 (2008)CrossRefGoogle ScholarPubMed
Daaboul, G. G., Vedula, R. S., Ahn, S., Lopez, C. A., Reddington, A., Ozkumur, E., and Ünlü, M. S., “LED-based Interferometric Reflectance Imaging Sensor for quantitative dynamic monitoring of biomolecular interactions,” Biosensors and Bioelectronics, Vol. 26, pp. 2221-2227 (2011)CrossRefGoogle ScholarPubMed
Sevenler, Derin, Lortlar Ünlü, Neşe, and Selim Ünlü, M, “Nanoparticle Biosensing With Interferometric Reflectance Imaging,” Nanobiosensors and Nanobioanalyses, Vestergaard, M.C., Kerman, K., Hsing, I.-M., Tamiya, E. (Eds.), Springer, ISBN 978-4-431-55189-8 (2015)Google Scholar
Zhuo, Y., Analyst, 139(5), 1007–1015 (2014)CrossRefGoogle Scholar
Vollmer, F. and Arnold, S., Nature methods, 5(7), 591–596 (2008)CrossRefGoogle Scholar
Reddington, A., Trueb, J. T., Freedman, D. S., Tuysuzoglu, A., Daaboul, G. G., Lopez, C. A., Karl, W. C., Connor, J. H., Fawcett, H. E., and Ünlü, M. S, “An Interferometric Reflectance Imaging Sensor for Point of Care Viral Diagnostics,” IEEE Transactions on Biomedical Engineering, Vol. 60, No. 12,, pp.3276–3283 (2013)CrossRefGoogle ScholarPubMed
See for example: Luchansky, M. S., Washburn, A. L., McClellan, M. S., Bailey, R., “Sensitive on-chip detection of a protein biomarker in human serum and plasma over an extended dynamic range using silicon photonic microring resonators and sub-micron beads,” Lab on a Chip. (2011) or P.E. Sheehan and L. J. Whitman “Detection limits for nanoscale biosensors,” Nano Letters, 5(4):803-7 (2005) CrossRefGoogle ScholarPubMed