Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators

Judith Su; Alexander FG Goldberg; Brian M Stoltz

doi:10.1038/lsa.2016.1

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Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators

Original Articles

- Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators
- Light: Science & Applications Vol. 5, Issue 1, (2016)
- Affiliations：
  
  1.Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  2.Divison of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA
- Author bio：
  
  J Su, Email: judy@caltech.edu
- Funds：
- DOI：10.1038/lsa.2016.1
  CLC：
- Published：2016-03，
  
  Published Online：22 August 2015，
  
  Received：06 March 2015，
  
  Revised：24 July 2015，
  
  Accepted：05 August 2015
- Accepted：
Scan QR Code
Su, J., Goldberg, A. F. G. & Stoltz, B. M. Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators. Light: Science & Applications, 5, e16001 (2016).
DOI：

Su, J., Goldberg, A. F. G. & Stoltz, B. M. Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators. Light: Science & Applications, 5, e16001 (2016). DOI： 10.1038/lsa.2016.1.

摘要

Abstract

Single-molecule detection is one of the fundamental challenges of modern biology. Such experiments often use labels that can be expensive

difficult to produce

and for small analytes

might perturb the molecular events being studied. Analyte size plays an important role in determining detectability. Here we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius

and 15.5 kDa molecules are detected in aqueous solution

thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the cell. Our results

covering several orders of magnitude of particle radius (100 nm to 2 nm)

agree with the 'reactive' model prediction for the frequency shift of the resonator upon particle binding. This confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed particle. We anticipate that our results will enable many applications

including more sensitive medical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time.

关键词

Keywords

biosensingfrequency lockinglabel-freemicrotoroidsingle molecule

references

Luchansky MS, Bailey RC. High-Q optical sensors for chemical and biological analysis.Anal Chem2011;84: 793–821..

Vollmer F, Arnold S. Whispering-gallery-mode biosensing: label-free detection down to single molecules.Nat Methods2008;5: 591–596..

Rodríguez-Lorenzo L, de la Rica R, Álvarez-Puebla RA, Liz-Marzán LM, Stevens MM. Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth.Nat Mater2012;11: 604–607..

Dantham VR, Holler S, Kolchenko V, Wan Z, Arnold S. Taking whispering gallery-mode single virus detection and sizing to the limit.Appl Phys Lett2012;101: 043704..

Dickson RM, Cubitt AB, Tsien RY, Moerner WE. On/off blinking and switching behaviour of single molecules of green fluorescent protein.Nature1997;388: 355–358..

Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DRet al. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations.Nat Biotechnol2010;28: 595–599..

Zijlstra P, Paulo PM, Orrit M. Optical detection of single non-absorbing molecules using the surface plasmon resonance of a gold nanorod.Nat Nanotechnol2012;7: 379–382..

Wiesendanger R.Scanning Probe Microscopy and Spectroscopy: Methods and Applications. Cambridge: Cambridge University Press; 1994; 244.

Swaim JD, Knittel J, Bowen WP. Detection of nanoparticles with a frequency locked whispering gallery mode microresonator.Appl Phys Lett2013;102: 183106..

Armani DK, Kippenberg TJ, Spillane SM, Vahala KJ. Ultra-high-Q toroid microcavity on a chip.Nature2003;421: 925–928..

Vahala KJ. Optical microcavities.Nature2003;424: 839–846..

Arnold S, Khoshsima M, Teraoka I, Holler S, Vollmer F. Shift of whispering-gallery modes in microspheres by protein adsorption.Opt Lett2003;28: 272–274..

Knight AE.Single Molecule Biology. London: Elsevier/Academic Press; 2009; ⅹⅸ.

Armani AM, Kulkarni RP, Fraser SE, Flagan RC, Vahala KJ. Label-free, single-molecule detection with optical microcavities.Science2007;317: 783–787..

Armani AM. Corrections and clarifications.Science2011;334: 1496..

Arnold S, Shopova SI, Holler S. Whispering gallery mode bio-sensor for label-free detection of single molecules: thermo-optic vs. reactive mechanism.Opt Express2010;18: 281–287..

Lu T, Lee H, Chen T, Herchak S, Kim JHet al. High sensitivity nanoparticle detection using optical microcavities.Proc Natl Acad Sci USA2011;108: 5976–5979..

He LN, Özdemir ŞK, Zhu JG, Kim W, Yang L. Detecting single viruses and nanoparticles using whispering gallery microlasers.Nat Nanotechnol2011;6: 428–432..

Vollmer F, Arnold S, Keng D. Single virus detection from the reactive shift of a whispering-gallery mode.Proc Natl Acad Sci USA2008;105: 20701–20704..

Zhu JG, Özdemir ŞK, He LN, Chen DR, Yang L. Single virus and nanoparticle size spectrometry by whispering-gallery-mode microcavities.Opt Express2011;19: 16195–16206..

Dantham VR, Holler S, Barbre C, Keng D, Kolchenko Vet al. Label-free detection of single protein using a nanoplasmonic-photonic hybrid microcavity.Nano Lett2013;13: 3347–3351..

Teng J, Dumon P, Bogaerts W, Zhang HB, Jian Xet al. Athermal silicon-on-insulator ring resonators by overlaying a polymer cladding on narrowed waveguides.Opt Express2009;17: 14627–14633..

Kerssemakers JWJ, Munteanu EL, Laan L, Noetzel TL, Janson MEet al. Assembly dynamics of microtubules at molecular resolution.Nature2006;442: 709–712..

Carter BC, Vershinin M, Gross SP. A comparison of step-detection methods: how well can you do?Biophys J2008;94: 306–319..

Gamba JM. The role of transport phenomena in whispering gallery mode optical biosensor performance. PhD thesis, California Institute of Technology, Pasadena, CA, 2012.

Ashkin A, Dziedzic JM, Bjorkholm JE, Chu S. Observation of a single-beam gradient force optical trap for dielectric particles.Opt Lett1986;11: 288–290..

Squires TM, Messinger RJ, Manalis SR. Making it stick: convection, reaction and diffusion in surface-based biosensors.Nat Biotechnol2008;26: 417–426..

Gamba JM, Flagan RC. Flow-enhanced transient response in whispering gallery mode biosensors.Appl Phys Lett2011;99: 253705..

Arnold S, Keng D, Shopova SI, Holler S, Zurawsky Wet al. Whispering gallery mode carousel – a photonic mechanism for enhanced nanoparticle detection in biosensing.Opt Express2009;17: 6230–6238..

Stern E, Klemic JF, Routenberg DA, Wyrembak PN, Turner-Evans DBet al. Label-free immunodetection with CMOS-compatible semiconducting nanowires.Nature2007;445: 519–522..

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