Abstract

We report on the applicability of combining surface-enhanced Raman scattering (SERS) with coherent anti-Stokes Raman scattering for high-sensitivity detection of biological molecules. We found that this combination of techniques provides more than 3 orders of signal enhancement compared with SERS and permits monitoring of biological molecules such as deoxyguanosine monophosphate (dGMP) and deoxyadenosine monophosphate at the single-molecule level. This combined technique also improved detection sensitivity for angiotensin peptide. As this is believed to be the first report of detection of dGMP at the single-molecule level, we suggest that this approach can serve as a new tool for biological studies.

© 2005 Optical Society of America

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    [CrossRef]

2004

2003

J. Jiang, K. Bosnick, M. Maillard, and L. Brus, J. Phys. Chem. B 107, 9964 (2003).
[CrossRef]

2002

2001

1999

A. Zumbusch, G. R. Holtom, and X. S. Xie, Phys. Rev. Lett. 82, 4142 (1999).
[CrossRef]

1998

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

1997

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

S. Nie and S. R. Emory, Science 275, 1102 (1997).
[CrossRef] [PubMed]

1994

E. J. Liang, A. Weippert, J.-M. Funk, A. Materny, and W. Kiefer, Chem. Phys. Lett. 227, 115 (1994).
[CrossRef]

1982

P. C. Lee and D. Meisel, J. Phys. Chem. 86, 3391 (1982).
[CrossRef]

1979

C. K. Chen, A. R.B. de Castro, Y. R. Shen, and F. DeMartini, Phys. Rev. Lett. 43, 946 (1979).
[CrossRef]

Berlin, A. A.

Book, L. D.

Bosnick, K.

J. Jiang, K. Bosnick, M. Maillard, and L. Brus, J. Phys. Chem. B 107, 9964 (2003).
[CrossRef]

Brus, L.

J. Jiang, K. Bosnick, M. Maillard, and L. Brus, J. Phys. Chem. B 107, 9964 (2003).
[CrossRef]

Chan, S.

Chen, C. K.

C. K. Chen, A. R.B. de Castro, Y. R. Shen, and F. DeMartini, Phys. Rev. Lett. 43, 946 (1979).
[CrossRef]

Cheng, J.-X.

Dasari, R. R.

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

de Castro, A. R.B.

C. K. Chen, A. R.B. de Castro, Y. R. Shen, and F. DeMartini, Phys. Rev. Lett. 43, 946 (1979).
[CrossRef]

Deinum, G.

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

DeMartini, F.

C. K. Chen, A. R.B. de Castro, Y. R. Shen, and F. DeMartini, Phys. Rev. Lett. 43, 946 (1979).
[CrossRef]

Emory, S. R.

S. Nie and S. R. Emory, Science 275, 1102 (1997).
[CrossRef] [PubMed]

Feld, M. S.

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

Funk, J.-M.

E. J. Liang, A. Weippert, J.-M. Funk, A. Materny, and W. Kiefer, Chem. Phys. Lett. 227, 115 (1994).
[CrossRef]

Holtom, G. R.

A. Zumbusch, G. R. Holtom, and X. S. Xie, Phys. Rev. Lett. 82, 4142 (1999).
[CrossRef]

Itzkan, I.

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

Jiang, J.

J. Jiang, K. Bosnick, M. Maillard, and L. Brus, J. Phys. Chem. B 107, 9964 (2003).
[CrossRef]

Jones, D. J.

Kall, M.

H. Xu and M. Kall, Phys. Rev. Lett. 89, 246802 (2002).
[CrossRef]

Kartha, V. B.

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

Kiefer, W.

E. J. Liang, A. Weippert, J.-M. Funk, A. Materny, and W. Kiefer, Chem. Phys. Lett. 227, 115 (1994).
[CrossRef]

Kneipp, H.

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

Kneipp, K.

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

Koo, T.-W.

Lee, P. C.

P. C. Lee and D. Meisel, J. Phys. Chem. 86, 3391 (1982).
[CrossRef]

Liang, E. J.

E. J. Liang, A. Weippert, J.-M. Funk, A. Materny, and W. Kiefer, Chem. Phys. Lett. 227, 115 (1994).
[CrossRef]

Maillard, M.

J. Jiang, K. Bosnick, M. Maillard, and L. Brus, J. Phys. Chem. B 107, 9964 (2003).
[CrossRef]

Manoharan, R.

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

Materny, A.

E. J. Liang, A. Weippert, J.-M. Funk, A. Materny, and W. Kiefer, Chem. Phys. Lett. 227, 115 (1994).
[CrossRef]

Meisel, D.

P. C. Lee and D. Meisel, J. Phys. Chem. 86, 3391 (1982).
[CrossRef]

Nie, S.

S. Nie and S. R. Emory, Science 275, 1102 (1997).
[CrossRef] [PubMed]

Perelman, L. T.

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

Potma, E.

Shen, Y. R.

C. K. Chen, A. R.B. de Castro, Y. R. Shen, and F. DeMartini, Phys. Rev. Lett. 43, 946 (1979).
[CrossRef]

Y. R. Shen, Principles of Nonlinear Optics (Wiley, New York, 1984).

Su, X.

Sun, L.

Wang, Y.

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

Weippert, A.

E. J. Liang, A. Weippert, J.-M. Funk, A. Materny, and W. Kiefer, Chem. Phys. Lett. 227, 115 (1994).
[CrossRef]

Xie, X. S.

Xu, H.

H. Xu and M. Kall, Phys. Rev. Lett. 89, 246802 (2002).
[CrossRef]

Ye, J.

Zhang, J.

Zumbusch, A.

A. Zumbusch, G. R. Holtom, and X. S. Xie, Phys. Rev. Lett. 82, 4142 (1999).
[CrossRef]

Appl. Spectrosc.

Chem. Phys. Lett.

E. J. Liang, A. Weippert, J.-M. Funk, A. Materny, and W. Kiefer, Chem. Phys. Lett. 227, 115 (1994).
[CrossRef]

J. Phys. Chem.

P. C. Lee and D. Meisel, J. Phys. Chem. 86, 3391 (1982).
[CrossRef]

J. Phys. Chem. B

J. Jiang, K. Bosnick, M. Maillard, and L. Brus, J. Phys. Chem. B 107, 9964 (2003).
[CrossRef]

Opt. Lett.

Phys. Rev. E

K. Kneipp, H. Kneipp, V. B. Kartha, R. Manoharan, G. Deinum, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. E 57, R6281 (1998).
[CrossRef]

Phys. Rev. Lett.

A. Zumbusch, G. R. Holtom, and X. S. Xie, Phys. Rev. Lett. 82, 4142 (1999).
[CrossRef]

C. K. Chen, A. R.B. de Castro, Y. R. Shen, and F. DeMartini, Phys. Rev. Lett. 43, 946 (1979).
[CrossRef]

K. Kneipp, Y. Wang, H. Kneipp, L. T. Perelman, I. Itzkan, R. R. Dasari, and M. S. Feld, Phys. Rev. Lett. 78, 1667 (1997).
[CrossRef]

H. Xu and M. Kall, Phys. Rev. Lett. 89, 246802 (2002).
[CrossRef]

Science

S. Nie and S. R. Emory, Science 275, 1102 (1997).
[CrossRef] [PubMed]

Other

Y. R. Shen, Principles of Nonlinear Optics (Wiley, New York, 1984).

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Figures (3)

Fig. 1
Fig. 1

Schematic diagram of the experimental setup. Two picosecond Ti:sapphire lasers, each generating 3-ps pulses at a 76-MHz repetition rate, are synchronized by a phase-locking device (SynchroLock AP, Coherent, Santa Clara, California). The polarization of the Stokes laser is modulated by a half-wave plate (HW). Two laser pulses are overlapped by a dichroic mirror (DM). The overlapped beam is focused onto a sample (S) by a microscope objective (MO). The backscattered SECARS signal is collected by the same objective, and both laser lines are blocked by a bandpass filter (BF). The filtered light is sent to a spectrometer, where the dispersion of light is recorded by a liquid-nitrogen-cooled CCD camera. The temporal overlap of laser pulses is monitored by the autocorrelator. LF, laser line filter; P, polarizer.

Fig. 2
Fig. 2

(a) SECARS spectra of single-molecule dAMP (90 pM) and of H 2 O as background. The SECARS signal of dAMP can be distinguished from the background by intensity. λ pump = 785 nm , λ Stokes = 833 nm . Each spectrum was collected for 100 ms. (b) Histogram of the intensities of the 734 - cm 1 SECARS signal of dAMP molecules. The multiple peaks are associated with the statistical presence of 0, 1, or 2 molecules in the probe volume, where one dAMP molecule is present on average. The curve is a fit with three Gaussian peaks.

Fig. 3
Fig. 3

(a) SECARS spectrum of single-molecule dGMP (90 pM) and SERS spectrum of dGMP (9 mM or 3 × 10 8 molecules in a probe volume). For SECARS, λ pump = 785 nm , λ Stokes = 827.7 nm . (b) SECARS spectrum of angiotensin ( 900 fg μ L or 8 molecules) and the SERS spectrum of angiotensin ( 9 ng μ L or 2 × 10 5 molecules). For SECARS, λ pump = 785 nm , λ Stokes = 852.4 nm . Each spectrum was collected for 100 ms.

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