Dynamic biological measurements require low light levels to avoid damaging the specimen. With this constraint on optical power, quantum noise fundamentally limits the measurement sensitivity. This limit can only be surpassed by extracting more information per photon by using quantum correlations. Here, we experimentally demonstrate that the quantum shot noise limit can be overcome for measurements of living systems. Quantum-correlated light with amplitude noise squeezed 75% below the vacuum level is used to perform microrheology experiments within Saccharomyces cerevisiae yeast cells. Naturally occurring lipid granules are tracked in real time as they diffuse through the cytoplasm, and the quantum noise limit is surpassed by 42%. The laser-based microparticle tracking technique used is compatible with non-classical light and is immune to low-frequency noise, leading the way to achieving a broad range of quantum-enhanced measurements in biology.
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Ashkin, A. & Dziedzic, J. Optical trapping and manipulation of viruses and bacteria. Science 235, 1517–1520 (1987).
Neuman, K. C. & Nagy, A. Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nature Methods 5, 491–505 (2008).
Greenleaf, W. J. & Block, S. M. Single-molecule, motion-based DNA sequencing using RNA polymerase. Science 5, 801 (2006).
Finer, J. T., Simmons, R. M. & Spudich, J. A. Single myosin molecule mechanics: piconewton forces and nanometre steps. Nature 313, 113–119 (1994).
Yamada, S., Wirtz, D. & Kuo, S. C. Mechanics of living cells measured by laser tracking microrheology. Biophys. J. 368, 1736–1747 (2000).
Senning, E. N. & Marcus, A. H. Actin polymerization driven mitochondrial transport in mating S. cerevisiae. Proc. Natl Acad. Sci. USA 78, 721–725 (2010).
Tolić-Nørrelykke, I. M., Munteanu, E-L., Thon, G., Oddershede, L. & Berg-Sørensen, K. Anomalous diffusion in living yeast cells. Phys. Rev. Lett. 93, 078102 (2004).
Selhuber-Unkel, C., Yde, P., Berg-Sørensen, K. & Oddershede, L. B. Variety in intracellular diffusion during the cell cycle. Phys. Biol. 6, 025015 (2009).
McGuinness, L. P. et al. Quantum measurement and orientation tracking of fluorescent nanodiamonds inside living cells. Nature Nanotech. 6, 358–363 (2011).
Crespi, A. et al. Measuring protein concentration with entangled photons. Appl. Phys. Lett. 100, 233704 (2012).
Nasr, M. B. et al. Quantum optical coherence tomography of a biological sample. Opt. Commun. 282, 1154–1159 (2009).
Tay, J. W., Hsu, M. T. L. & Bowen, W. P. Quantum limited particle sensing in optical tweezers. Phys. Rev. A 80, 063806 (2009).
Giovannetti, V., Lloyd, S. & Maccone, L. Quantum-enhanced measurements: beating the standard quantum limit. Science 306, 1330–1336 (2004).
Demkowicz-Dobrzański, R., Kołodyński, J. & Guţǎ, M. The elusive Heisenberg limit in quantum-enhanced metrology. Nature Commun. 3, 1063 (2012).
Abadie, J. et al. A gravitational wave observatory operating beyond the quantum shot-noise limit. Nature Phys. 7, 962–965 (2011).
Wolfgramm, F. et al. Squeezed-light optical magnetometry. Phys. Rev. Lett. 105, 053601 (2010).
Nagata, T., Okamoto, R., O'Brien, J. L., Sasaki, K. & Takeuchi, S. Beating the standard quantum limit with four-entangled photons. Science 316, 726–729 (2007).
Kolobov, M. I. & Fabre, C. Quantum limits on optical resolution. Phys. Rev. Lett. 85, 3789–3792 (2000).
McKenzie, K. et al. Squeezing in the audio gravitational-wave detection band. Phys. Rev. Lett. 93, 161105 (2004).
Yurke, B., Grangier, P. & Slusher, R. E. Squeezed-state enhanced two-frequency interferometry. J. Opt. Soc. Am. B 4, 1677–1682 (1987).
Franosch, T. et al. Resonances arising from hydrodynamic memory in Brownian motion. Nature 478, 85–88 (2011).
Treps, N. et al. A quantum laser pointer. Science 301, 940–943 (2003).
Peterman, E. J., Gittes, F. & Schmidt, C. F. Laser-induced heating in optical traps. Biophys. J. 84, 1308–1316 (2003).
Mason, T. G. Estimating the viscoelastic moduli of complex fluids using the generalized Stokes–Einstein equation. Rheol. Acta 39, 371–378 (2000).
Taylor, M. A., Knittel, J., Hsu, M. T. L., Bachor, H-A. & Bowen, W. P. Sagnac interferometer-enhanced particle tracking in optical tweezers. J. Opt. 13, 044014 (2011).
Neuman, K. C., Chadd, E. H., Liou, G. F., Bergman, K. & Block, S. M. Characterization of photodamage to Escherichia coli in optical traps. Biophys. J. 77, 2856–2863 (1999).
Chavez, I., Huang, R., Henderson, K., Florin, E-L. & Raizen, M. G. Development of a fast position-sensitive laser beam detector. Rev. Sci. Instrum. 79, 105104 (2008).
Taylor, M. A., Knittel, J. & Bowen, W. P. Fundamental constraints on particle tracking with optical tweezers. Preprint at http://arxiv.org/abs/1208.0657 (2012).
Buchanan, M., Atakhorrami, M., Palierne, J. F., MacKintosh, F. C. & Schmidt, C. F. High-frequency microrheology of wormlike micelles. Phys. Rev. E 72, 011504 (2005).
Huang, R. et al. Direct observation of the full transition from ballistic to diffusive Brownian motion in a liquid. Nature Phys. 7, 576–580 (2011).
Chang, D. E. et al. Cavity opto-mechanics using an optically levitated nanosphere. Proc. Natl Acad. Sci. USA 107, 1005–1010 (2010).
Brida, G., Genovese, M. & Ruo Berchera, I. Experimental realization of sub-shot-noisequantum imaging. Nature Photon. 4, 227–230 (2010).
The authors thank Ping Koy Lam for facilitating the squeezing experiments, Bill Williams and Nicolas Treps for useful discussions about microrheology and spatial squeezing respectively, and Magnus Hsu for input on the experiments. This work was supported by the Australian Research Council Discovery Project (contract no. DP0985078). B.H. acknowledges financial support from the Alexander von Humboldt Foundation.
The authors declare no competing financial interests.
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Taylor, M., Janousek, J., Daria, V. et al. Biological measurement beyond the quantum limit. Nature Photon 7, 229–233 (2013). https://doi.org/10.1038/nphoton.2012.346
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