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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 3, Iss. 5 — May. 1, 2012
  • pp: 854–862
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Cross-phase modulation spectral shifting: nonlinear phase contrast in a pump-probe microscope

Jesse W. Wilson, Prathyush Samineni, Warren S. Warren, and Martin C. Fischer  »View Author Affiliations


Biomedical Optics Express, Vol. 3, Issue 5, pp. 854-862 (2012)
http://dx.doi.org/10.1364/BOE.3.000854


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Abstract

Microscopy with nonlinear phase contrast is achieved by a simple modification to a nonlinear pump-probe microscope. The technique measures cross-phase modulation by detecting a pump-induced spectral shift in the probe pulse. Images with nonlinear phase contrast are acquired both in transparent and absorptive media. In paraffin-embedded biopsy sections, cross-phase modulation complements the chemically-specific pump-probe images with structural context.

© 2012 OSA

1. Introduction

Nonlinear pump-probe microscopy enables label-free, chemically specific imaging of absorptive pigments such as oxy- and deoxy-hemoglobin in microvasculature [1

1. D. Fu, T. E. Matthews, T. Ye, I. R. Piletic, and W. S. Warren, “Label-free in vivo optical imaging of microvasculature and oxygenation level,” J. Biomed. Opt. 13(4), 040503 (2008). [CrossRef] [PubMed]

], eumelanin and pheomelanin in pigmented lesions such as melanomas [2

2. T. E. Matthews, I. R. Piletic, M. A. Selim, M. J. Simpson, and W. S. Warren, “Pump-probe imaging differentiates melanoma from melanocytic nevi,” Sci. Transl. Med. 3(71), 71ra15 (2011). [CrossRef] [PubMed]

,3

3. P. Samineni, A. deCruz, T. E. Villafaña, W. S. Warren, and M. C. Fischer, “Pump-probe imaging of historical pigments used in paintings,” Opt. Lett. , doc. ID 160175 (posted 29 February 2012, in press).

], and even historical pigments in artwork [3

3. P. Samineni, A. deCruz, T. E. Villafaña, W. S. Warren, and M. C. Fischer, “Pump-probe imaging of historical pigments used in paintings,” Opt. Lett. , doc. ID 160175 (posted 29 February 2012, in press).

]. The interpretation of a pump-probe image may be enhanced by structural context from a complementary imaging modality. Recently, complementary information from four wave mixing (4WM) has been shown to resolve ambiguities in interpreting third harmonic generation (THG) images [4

4. P. Mahou, N. Olivier, G. Labroille, L. Duloquin, J.-M. Sintes, N. Peyriéras, R. Legouis, D. Débarre, and E. Beaurepaire, “Third-harmonic generation, four-wave mixing microscopy of tissues and embryos,” Biomed. Opt. Express 2(10), 2837–2849 (2011). [CrossRef] [PubMed]

]. In pump-probe interactions, the same nonlinear optical property that enables 4WM—the real part of the third-order optical susceptibility χ(3)—gives rise to cross-phase modulation (XPM). XPM is sometimes viewed as an artifact inpump-probe spectroscopy [5

5. K. Ekvall, P. van der Meulen, C. Dhollande, L.-E. Berg, S. Pommeret, R. Naskrecki, and J.-C. Mialocq, “Cross phase modulation artifact in liquid phase transient absorption spectroscopy,” J. Appl. Phys. 87(5), 2340 (2000). [CrossRef]

] (which can be suppressed by using a high numerical aperture condenser [6

6. C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008). [CrossRef] [PubMed]

]). Here we demonstrate that simple modifications to a pump-probe microscope enable a new technique, cross-phase modulation spectral shifting (XPMSS), which can complement pump-probe microscopy with structural information even in situations where linear techniques (i.e. linear transmittance and confocal reflectance) are obscured by scattering.

2. Setup and theory

The experimental arrangement employs a standard pump-probe configuration, shown in Fig. 1
Fig. 1 The optical set-up for XPMSS imaging involves adding a shortpass filter to an existing pump-probe microscope. Optionally a balanced photodiode can be used to isolate nonlinear phase modulation from nonlinear absorption.
, where the pump is modulated at 1 MHz with an acousto-optic modulator (AOM), and a motorized delay stage controls pump-probe delay, τ. Probe and pump pulses are supplied by a Ti:sapph oscillator (Spectra-Physics Tsunami), and an intracavity-doubled optical parametric oscillator (Coherent Mira OPO), capable of providing pump and probe wavelength combinations from 520 nm down to 880 nm. The pump and probe pulses are focused onto a sample with a microscope objective (here we use either a 10x / 0.25 NA dry or a 40x / 0.8 NA water immersion) and re-collimated afterwards by 1.1 NA condenser (the high-NA condenser helps to minimize artifacts from thermal lensing and Kerr lensing [6

6. C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008). [CrossRef] [PubMed]

]).

Cross-phase modulation (XPM) shifts the probe pulse spectrum in a manner that depends on the pump-probe delay τ [11

11. G. P. Agrawal, P. L. Baldeck, and R. R. Alfano, “Temporal and spectral effects of cross-phase modulation on copropagating ultrashort pulses in optical fibers,” Phys. Rev. A 40(9), 5063–5072 (1989). [CrossRef] [PubMed]

]. This shift may be detected by splitting the probe pulse at its center wavelength, and looking for an imbalance between the two spectral halves. After the condenser, the pump is rejected and the probe beam is split at its center wavelength by a dielectric filter (Chroma D800/20m), angle-tuned to set the filter cutoff at the center of the probe spectrum. The transmitted half of the probe spectrum is directed onto a photodiode. Any shift Δω in the probe spectrum caused by XPM interaction with the modulated pump results in 1 MHz modulation of the probe intensity transmitted through the filter; this signal is detected with a lock-in amplifier. Optionally, a high-speed balanced photodiode (NewFocus model 2307) may be used to suppress other nonlinear pump-probe interactions that do not shift the probe spectrum (such as nonlinear absorption).

As the probe pulse propagates through the sample, it accumulates phase from both the linear and nonlinear indexes of refraction:
φ(t)=[n0+n2,SPMIpr(t)+n2,XPMIpu(t)]ωprLc.
(1)
Here, n0 is the linear index of refraction, n2,SPMRe{χ(3)(pr; ωpr, ω pr, -ωpr)} is the nonlinear index mediating self-phase modulation, n2,XPMRe{χ(3)(pr; ω pr, ωpu, -ωpu)} is the nonlinear index mediating cross-phase modulation, I{pu,pr}(t) are the pump and probe pulse temporal intensity profiles, ω{pu,pr} are the pump and probe angular frequencies, L is the effective interaction length, and c is the velocity of light in vacuum. The pump-induced XPM term, n2,XPMIpu(t), may be isolated from the other terms by modulating the pump with an AOM, then filtering the photodiode’s output with a lock-in amplifier.

To roughly estimate the expected signal amplitude, consider a pump-probe delay τ such that the peak of the probe pulse coincides with the steepest slope of the pump pulse (on either the rising or the falling half of the pump pulse). The resulting XPM may be approximately regarded as linear across the probe pulse in time; this linear temporal phase produces a spectral shift in the probe:
Δω=dφdt=ωprcLn2,XPM(dIpudt)t=τ.
(2)
The change in detected intensity (on a single photodiode) in a spectrally shifted probe is
ΔS=ω0Ipr(ω)dωω0Ipr(ωΔω)dω=0ΔωIpr(ω)dω=I0erf(tfwhmΔω2ln2).
(3)
For a balanced detector, the intensity incident on one photodiode increases by ΔS, while the intensity incident on the other photodiode decreases by ΔS; the total signal in this case is 2ΔS.

Consider the case where both pump and probe pulses have Gaussian intensity profiles with full-width at half maximum duration tfwhm. Centering the probe on the rising slope of the pump shifts the probe to higher frequency; centering the probe on the falling slope of the pump shifts the probe to lower frequency. The maximum spectral shift will be imparted atτ=tfwhm/8ln2, where
(dIpudt)max=I08ln2e1tfwhm.
(4)
Of course, this shift applied to only a small portion of the pulse. A more precise numerical calculation is straightforward with the exact pulse shape, as discussed later, but other factors affect the measurement (such as beam spatial mode quality, residual uncompensated dispersion, and spatial overlap) [12

12. P. Chapple, J. Staromlynska, J. Hermann, T. Mckay, and R. McDuff, “Single-beam Z-scan: measurement techniques and analysis,” J. Nonlinear Opt. Phys. Mater. 6(3), 251–294 (1997). [CrossRef]

] so this is only an estimate.

3. Results

3.1 Pump-probe spectroscopy / transient response

To demonstrate the spectral shifting based XPM measurement technique and to show that a balanced photodiode effectively subtracts nonlinear absorption we performed pump-probe delay scans of rhodamine-6G (R6G), chosen for its strong nonlinear absorption cross-section (15 GM at 800 nm, 27.5 GM at 750 nm, and 5 GM at 650 nm [13

13. P. Tian and W. S. Warren, “Ultrafast measurement of two-photon absorption by loss modulation,” Opt. Lett. 27(18), 1634–1636 (2002). [CrossRef] [PubMed]

15

15. Reference [14] defined the TPA cross section with an extra factor of two that is divided out here for direct comparison to the value in Ref. [13].

]). We compare pure methanol and a 30 mM solution of R6G in methanol using a simplified optical set-up outside the microscope, in which the combined beams are directly focused into a cuvette of 1 mm path length by a 10x 0.25 NA objective (back aperture underfilled by 30%, NAeff = 0.075). The pump and probe pulses used in these measurements were both of approximately 175 fs duration (estimated from the cross-correlation shown in Fig. 2(a)
Fig. 2 (a) Pump-probe delay scan of 5 mM R6G in methanol, single photodiode without the probe shortpass edge filter. (b) Scan of 30 mM R6G in methanol, single photodiode with the probe shortpass edge filter. (c) XPMSS delay scans of methanol and 30 mM R6G dissolved in methanol with balanced photodiode. Though R6G has a large nonlinear absorption cross section, the balanced photodiode robustly measures XPM spectral shift, rejecting amplitude modulation
): pump wavelength of 672 nm with 16 mW average power; probe wavelength of 794 nm with 18 mW average power.

The resulting data in Fig. 2 show pump-probe delay scans for several different conditions. Figure 2(a) shows a standard pump-probe delay scan of 5 mM R6G with a single photodiode and only the pump rejection filter (no shortpass filter) before the photodiode. With the selected pump-probe wavelengths, this reflects sum-frequency absorption when the pulses are overlapped; the resulting delay scan is essentially a cross-correlation of the pump and probe pulses. In Fig. 2(b), the experiment is repeated with 30 mM R6G and the addition of a 792 nm shortpass filter to split the probe spectrum in front of the single photodiode; at this concentration, the nonlinear absorption in the dye completely overwhelms any XPMSS signal. However, Fig. 2(c) demonstrates this nonlinear absorption is cancelled when a balanced photodiode is employed. The XPMSS pump-probe delay scans exhibit a characteristic dispersive shape, since alignment of the probe with the rising or falling slopes of the pump pulse shifts the spectrum in opposite directions. Each delay scan took less than a minute to acquire, and has a signal to noise ratio of ~250 (calculated as the peak value divided by the standard deviation of the signal for τ > 0.5 ps, where there is no pump-probe overlap).

To compare the experimental results in Fig. 2(c) with theory, a back-of the envelope estimate of the XPMSS signal follows. The pump pulse peak intensity under these focal conditions is I0 = 77 GW/cm2. The maximum slope of the pump pulse is 5.3 TW∙cm−2∙ps−1. The nonlinear refractive index of methanol is n2≈3 × 10−16 cm2/W [16

16. E. T. J. Nibbering, M. A. Franco, B. S. Prade, G. Grillon, C. Le Blanc, and A. Mysyrowicz, “Measurement of the nonlinear refractive index of transparent materials by spectral analysis after nonlinear propagation,” Opt. Commun. 119(5-6), 479–484 (1995). [CrossRef]

]. The signal on the balanced photodiode for half of the spectrum is 0.64 V (taking into consideration the Si detector sensitivity of 0.5 A/W at 800 nm, 1.4 V/mA amplifier gain at 1 MHz, and an ND filter with 1.0 OD in front of the detector). We numerically compute the spectral shift the probe by applying a Gaussian phase, offset in time by τ, resulting in an expected shift of 3.7 × 10−4 nm, which will yield a lock-in signal amplitude of 28 μVRMS. As mentioned above, this is an upper limit on the XPMSS signal; factors such as imperfect spatial overlap reduce the signal observed in experiment.

3.2 Live cell imaging with cross-phase modulation

In Fig. 3
Fig. 3 XPM spectral shifting in a fresh onion epidermis with a 10x 0.25 NA objective. (a) Image at a single delay, −100 fs. (b) Delay scans for regions of interest in cytoplasm (blue curve) and cell wall (red curve); both exhibit spectral shifting characteristic of cross-phase modulation. (c) contrast enhanced by subtracting the images taken at the two delays with peak XPM spectral shifting response (at −100 fs and + 100 fs). (d) transmissivity image for comparison. Appx. 7 seconds per frame, 83 mW total power incident at sample.
we image a single layer of epidermal cells from an onion with pump and probe wavelengths of 720 nm and 810 nm, respectively. An image stack is acquired as a function of varying pump-probe delay τ to confirm that the spectrally filtered probe signal has the same dispersive profile expected of an XPMSS measurement. Figure 3(a) shows a single image acquired at τ = 100 fs, found to give the maximum spectral shift. To show the XPMSS dispersive time delay profile, two regions of interest are highlighted; the averaged delay scans for each region is shown in Fig. 3(b), in good agreement with what we expect from Fig. 2(c). The contrast available with XPMSS can be doubled by subtracting the signal at the negative XPMSS peak (t = −100fs) from the signal at the positive XPMSS peak (t = −100 fs); this XPMSS difference image is shown in Fig. 3(c). For comparison, the linear transmissivity image is shown in Fig. 3(d).

The total optical power employed here was 83 mW—enough to warrant consideration of damage to the cells under study. In this regime (~100 fs duration, 80 MHz pulses of near-infrared wavelength), the primary concern is from accumulation of chemical damage triggered by laser-induced low-density plasma formation [17

17. A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, “Mechanisms of femtosecond laser nanosurgery of cells and tissues,” Appl. Phys. B 81(8), 1015–1047 (2005). [CrossRef]

]. The intensity at which the free electron density reaches an average of one free electron per focal volume is as low as 0.26 TW/cm2 [17

17. A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, “Mechanisms of femtosecond laser nanosurgery of cells and tissues,” Appl. Phys. B 81(8), 1015–1047 (2005). [CrossRef]

], and cell death through apoptosis has been demonstrated with as little as 0.44 TW/cm2 [18

18. U. K. Tirlapur, K. König, C. Peuckert, R. Krieg, and K. J. Halbhuber, “Femtosecond near-infrared laser pulses elicit generation of reactive oxygen species in mammalian cells leading to apoptosis-like death,” Exp. Cell Res. 263(1), 88–97 (2001). [CrossRef] [PubMed]

]. For the images in Fig. 3, the peak intensity is lower than both these numbers: 83 mW through a 0.25 NA, underfilled by 72% (NAeff = 0.18) objective, is 0.18 TW/cm2, comparable to the safe intensity level of 0.12 TW/cm2 reported in Ref [19

19. K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, “Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes,” Opt. Lett. 22(2), 135–136 (1997). [CrossRef] [PubMed]

].

3.3 Melanoma biopsy imaging

In situations where pigmentation is less dense, the dot product analysis alone may be sufficient to separate XPMSS from transient absorption without the need for a balanced detector. To demonstrate this, we imaged a wider field of view of the dermo-epidermal junction in an unstained biopsy section of a melanoma using a normal photodiode. The pump-probe image is shown in Fig. 5(a)
Fig. 5 Images of the dermo-epidermal junction in a melanoma biopsy. a) Pump-probe image showing uniform eumelanin content. b) Combined multiphoton autofluorescence and SHG (imaged with a single PMT). c) XPMSS dot product image. Images acquired with a 40x 0.8 NA water immersion objective, 5 mW 720 nm pump, 5 mW 810 nm probe, 49 delays, 4 frame averaging.
, and for comparison with other commonly employed nonlinear methods for dermatological imaging, Fig. 5(b) shows an image of second harmonic generation (SHG) and multiphoton autofluorescence (both acquired episcopically with a single PMT behind a 680 nm dichroic and a BG40 glass filter). Figure 5(c) shows the XPMSS dot product image, generated with the same technique used for Fig. 4(d). As with the image of the single pigmented cell, the pump-probe image here shows uniform eumelanin content. This pigment-specific image is complemented by structural details in both the autofluorescence/SHG and XPMSS images. The SHG signal originates in the dermal collagen, and is an order of magnitude more intense than the epidermal autofluorescence signal. In the XPMSS image, fine details are observed in the dermal collagen, and outlines of cell nuclei can be discerned. Here, the XPMSS dot product clearly separates XPMSS from the excited state absorption response of eumelanin, even without balanced detection.

4. Conclusions

In addition to providing complementary structural contrast in pump-probe imaging, there are numerous potential applications of XPMSS both for imaging and nonlinear spectroscopy. First, the high sensitivity of XPMSS may be able to sense changes in ion concentration. Studies with third harmonic generation (THG) have confirmed that χ(3) depends on ion concentration, though THG images are more sensitive to cell geometry than to actual ion concentration [22

22. D. Débarre and E. Beaurepaire, “Quantitative characterization of biological liquids for third-harmonic generation microscopy,” Biophys. J. 92(2), 603–612 (2007). [CrossRef] [PubMed]

]. However, 4WM and XPM are sensitive to the third-order susceptibility itself, and may provide a more direct measurement of ion concentration. This application may lead to label-free optical imaging of neuronal activity [23

23. M. C. Fischer, H. C. Liu, I. R. Piletic, Y. Escobedo-Lozoya, R. Yasuda, and W. S. Warren, “Self-phase modulation signatures of neuronal activity,” Opt. Lett. 33(3), 219–221 (2008). [CrossRef] [PubMed]

]. Second, XPMSS may be useful for imaging optically cleared specimens. Most fluorescent labels bleach with repetitive imaging. Special care must be taken to preserve fluorescence in the process of specimen preservation and optical clearing. The fluorophores that survive the clearing process are only good for a limited amount of imaging, as the excitation light causes photobleaching [24

24. H. S. Sakhalkar, M. Dewhirst, T. Oliver, Y. Cao, and M. Oldham, “Functional imaging in bulk tissue specimens using optical emission tomography: fluorescence preservation during optical clearing,” Phys. Med. Biol. 52(8), 2035–2054 (2007). [CrossRef] [PubMed]

]. In pump-probe spectroscopy, XPMSS characterization could help clean up unwanted coherent artifacts near time-zero [5

5. K. Ekvall, P. van der Meulen, C. Dhollande, L.-E. Berg, S. Pommeret, R. Naskrecki, and J.-C. Mialocq, “Cross phase modulation artifact in liquid phase transient absorption spectroscopy,” J. Appl. Phys. 87(5), 2340 (2000). [CrossRef]

]. In z-scan measurements with high repetition rate lasers, which rely on sensing changes in spatial mode, it is challenging to separate the desired n2 Kerr lensing from thermal lensing [25

25. A. Gnoli, L. Razzari, and M. Righini, “Z-scan measurements using high repetition rate lasers: how to manage thermal effects,” Opt. Express 13(20), 7976–7981 (2005). [CrossRef] [PubMed]

]; in the XPMSS method, because thermal diffusion timescales are orders of magnitude longer than the < 1 picosecond timescale of the temporal phase modulation, thermal effects are readily separable. Finally, XPMSS could also be used to measure off-diagonal tensor elements of the third-order susceptibility χ(3) by rotating the polarization of the pump and probe pulses.

Acknowledgments

This study was funded by the Duke University and the NIH (grant no. 1RC1CA145105).

References and links

1.

D. Fu, T. E. Matthews, T. Ye, I. R. Piletic, and W. S. Warren, “Label-free in vivo optical imaging of microvasculature and oxygenation level,” J. Biomed. Opt. 13(4), 040503 (2008). [CrossRef] [PubMed]

2.

T. E. Matthews, I. R. Piletic, M. A. Selim, M. J. Simpson, and W. S. Warren, “Pump-probe imaging differentiates melanoma from melanocytic nevi,” Sci. Transl. Med. 3(71), 71ra15 (2011). [CrossRef] [PubMed]

3.

P. Samineni, A. deCruz, T. E. Villafaña, W. S. Warren, and M. C. Fischer, “Pump-probe imaging of historical pigments used in paintings,” Opt. Lett. , doc. ID 160175 (posted 29 February 2012, in press).

4.

P. Mahou, N. Olivier, G. Labroille, L. Duloquin, J.-M. Sintes, N. Peyriéras, R. Legouis, D. Débarre, and E. Beaurepaire, “Third-harmonic generation, four-wave mixing microscopy of tissues and embryos,” Biomed. Opt. Express 2(10), 2837–2849 (2011). [CrossRef] [PubMed]

5.

K. Ekvall, P. van der Meulen, C. Dhollande, L.-E. Berg, S. Pommeret, R. Naskrecki, and J.-C. Mialocq, “Cross phase modulation artifact in liquid phase transient absorption spectroscopy,” J. Appl. Phys. 87(5), 2340 (2000). [CrossRef]

6.

C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science 322(5909), 1857–1861 (2008). [CrossRef] [PubMed]

7.

M. C. Fischer, T. Ye, G. Yurtsever, A. Miller, M. Ciocca, W. Wagner, and W. S. Warren, “Two-photon absorption and self-phase modulation measurements with shaped femtosecond laser pulses,” Opt. Lett. 30(12), 1551–1553 (2005). [CrossRef] [PubMed]

8.

M. C. Fischer, H. C. Liu, I. R. Piletic, and W. S. Warren, “Simultaneous self-phase modulation and two-photon absorption measurement by a spectral homodyne Z-scan method,” Opt. Express 16(6), 4192–4205 (2008). [CrossRef] [PubMed]

9.

P. Samineni, Z. Perret, W. S. Warren, and M. C. Fischer, “Measurements of nonlinear refractive index in scattering media,” Opt. Express 18(12), 12727–12735 (2010). [CrossRef] [PubMed]

10.

P. Samineni, B. Li, J. W. Wilson, W. S. Warren, and M. C. Fischer, “Cross-phase modulation imaging,” Opt. Lett. 37(5), 800–802 (2012). [CrossRef] [PubMed]

11.

G. P. Agrawal, P. L. Baldeck, and R. R. Alfano, “Temporal and spectral effects of cross-phase modulation on copropagating ultrashort pulses in optical fibers,” Phys. Rev. A 40(9), 5063–5072 (1989). [CrossRef] [PubMed]

12.

P. Chapple, J. Staromlynska, J. Hermann, T. Mckay, and R. McDuff, “Single-beam Z-scan: measurement techniques and analysis,” J. Nonlinear Opt. Phys. Mater. 6(3), 251–294 (1997). [CrossRef]

13.

P. Tian and W. S. Warren, “Ultrafast measurement of two-photon absorption by loss modulation,” Opt. Lett. 27(18), 1634–1636 (2002). [CrossRef] [PubMed]

14.

N. S. Makarov, M. Drobizhev, and A. Rebane, “Two-photon absorption standards in the 550-1600 nm excitation wavelength range,” Opt. Express 16(6), 4029–4047 (2008). [CrossRef] [PubMed]

15.

Reference [14] defined the TPA cross section with an extra factor of two that is divided out here for direct comparison to the value in Ref. [13].

16.

E. T. J. Nibbering, M. A. Franco, B. S. Prade, G. Grillon, C. Le Blanc, and A. Mysyrowicz, “Measurement of the nonlinear refractive index of transparent materials by spectral analysis after nonlinear propagation,” Opt. Commun. 119(5-6), 479–484 (1995). [CrossRef]

17.

A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, “Mechanisms of femtosecond laser nanosurgery of cells and tissues,” Appl. Phys. B 81(8), 1015–1047 (2005). [CrossRef]

18.

U. K. Tirlapur, K. König, C. Peuckert, R. Krieg, and K. J. Halbhuber, “Femtosecond near-infrared laser pulses elicit generation of reactive oxygen species in mammalian cells leading to apoptosis-like death,” Exp. Cell Res. 263(1), 88–97 (2001). [CrossRef] [PubMed]

19.

K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, “Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes,” Opt. Lett. 22(2), 135–136 (1997). [CrossRef] [PubMed]

20.

I. R. Piletic, T. E. Matthews, and W. S. Warren, “Probing near-infrared photorelaxation pathways in eumelanins and pheomelanins,” J. Phys. Chem. A 114(43), 11483–11491 (2010). [CrossRef] [PubMed]

21.

R. Lazova and J. M. Pawelek, “Why do melanomas get so dark?” Exp. Dermatol. 18(11), 934–938 (2009). [CrossRef] [PubMed]

22.

D. Débarre and E. Beaurepaire, “Quantitative characterization of biological liquids for third-harmonic generation microscopy,” Biophys. J. 92(2), 603–612 (2007). [CrossRef] [PubMed]

23.

M. C. Fischer, H. C. Liu, I. R. Piletic, Y. Escobedo-Lozoya, R. Yasuda, and W. S. Warren, “Self-phase modulation signatures of neuronal activity,” Opt. Lett. 33(3), 219–221 (2008). [CrossRef] [PubMed]

24.

H. S. Sakhalkar, M. Dewhirst, T. Oliver, Y. Cao, and M. Oldham, “Functional imaging in bulk tissue specimens using optical emission tomography: fluorescence preservation during optical clearing,” Phys. Med. Biol. 52(8), 2035–2054 (2007). [CrossRef] [PubMed]

25.

A. Gnoli, L. Razzari, and M. Righini, “Z-scan measurements using high repetition rate lasers: how to manage thermal effects,” Opt. Express 13(20), 7976–7981 (2005). [CrossRef] [PubMed]

OCIS Codes
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(190.7110) Nonlinear optics : Ultrafast nonlinear optics
(180.4315) Microscopy : Nonlinear microscopy

ToC Category:
Microscopy

History
Original Manuscript: March 9, 2012
Revised Manuscript: April 1, 2012
Manuscript Accepted: April 3, 2012
Published: April 4, 2012

Citation
Jesse W. Wilson, Prathyush Samineni, Warren S. Warren, and Martin C. Fischer, "Cross-phase modulation spectral shifting: nonlinear phase contrast in a pump-probe microscope," Biomed. Opt. Express 3, 854-862 (2012)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-3-5-854


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References

  1. D. Fu, T. E. Matthews, T. Ye, I. R. Piletic, and W. S. Warren, “Label-free in vivo optical imaging of microvasculature and oxygenation level,” J. Biomed. Opt.13(4), 040503 (2008). [CrossRef] [PubMed]
  2. T. E. Matthews, I. R. Piletic, M. A. Selim, M. J. Simpson, and W. S. Warren, “Pump-probe imaging differentiates melanoma from melanocytic nevi,” Sci. Transl. Med.3(71), 71ra15 (2011). [CrossRef] [PubMed]
  3. P. Samineni, A. deCruz, T. E. Villafaña, W. S. Warren, and M. C. Fischer, “Pump-probe imaging of historical pigments used in paintings,” Opt. Lett., doc. ID 160175 (posted 29 February 2012, in press).
  4. P. Mahou, N. Olivier, G. Labroille, L. Duloquin, J.-M. Sintes, N. Peyriéras, R. Legouis, D. Débarre, and E. Beaurepaire, “Third-harmonic generation, four-wave mixing microscopy of tissues and embryos,” Biomed. Opt. Express2(10), 2837–2849 (2011). [CrossRef] [PubMed]
  5. K. Ekvall, P. van der Meulen, C. Dhollande, L.-E. Berg, S. Pommeret, R. Naskrecki, and J.-C. Mialocq, “Cross phase modulation artifact in liquid phase transient absorption spectroscopy,” J. Appl. Phys.87(5), 2340 (2000). [CrossRef]
  6. C. W. Freudiger, W. Min, B. G. Saar, S. Lu, G. R. Holtom, C. He, J. C. Tsai, J. X. Kang, and X. S. Xie, “Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy,” Science322(5909), 1857–1861 (2008). [CrossRef] [PubMed]
  7. M. C. Fischer, T. Ye, G. Yurtsever, A. Miller, M. Ciocca, W. Wagner, and W. S. Warren, “Two-photon absorption and self-phase modulation measurements with shaped femtosecond laser pulses,” Opt. Lett.30(12), 1551–1553 (2005). [CrossRef] [PubMed]
  8. M. C. Fischer, H. C. Liu, I. R. Piletic, and W. S. Warren, “Simultaneous self-phase modulation and two-photon absorption measurement by a spectral homodyne Z-scan method,” Opt. Express16(6), 4192–4205 (2008). [CrossRef] [PubMed]
  9. P. Samineni, Z. Perret, W. S. Warren, and M. C. Fischer, “Measurements of nonlinear refractive index in scattering media,” Opt. Express18(12), 12727–12735 (2010). [CrossRef] [PubMed]
  10. P. Samineni, B. Li, J. W. Wilson, W. S. Warren, and M. C. Fischer, “Cross-phase modulation imaging,” Opt. Lett.37(5), 800–802 (2012). [CrossRef] [PubMed]
  11. G. P. Agrawal, P. L. Baldeck, and R. R. Alfano, “Temporal and spectral effects of cross-phase modulation on copropagating ultrashort pulses in optical fibers,” Phys. Rev. A40(9), 5063–5072 (1989). [CrossRef] [PubMed]
  12. P. Chapple, J. Staromlynska, J. Hermann, T. Mckay, and R. McDuff, “Single-beam Z-scan: measurement techniques and analysis,” J. Nonlinear Opt. Phys. Mater.6(3), 251–294 (1997). [CrossRef]
  13. P. Tian and W. S. Warren, “Ultrafast measurement of two-photon absorption by loss modulation,” Opt. Lett.27(18), 1634–1636 (2002). [CrossRef] [PubMed]
  14. N. S. Makarov, M. Drobizhev, and A. Rebane, “Two-photon absorption standards in the 550-1600 nm excitation wavelength range,” Opt. Express16(6), 4029–4047 (2008). [CrossRef] [PubMed]
  15. Reference [14] defined the TPA cross section with an extra factor of two that is divided out here for direct comparison to the value in Ref. [13].
  16. E. T. J. Nibbering, M. A. Franco, B. S. Prade, G. Grillon, C. Le Blanc, and A. Mysyrowicz, “Measurement of the nonlinear refractive index of transparent materials by spectral analysis after nonlinear propagation,” Opt. Commun.119(5-6), 479–484 (1995). [CrossRef]
  17. A. Vogel, J. Noack, G. Hüttman, and G. Paltauf, “Mechanisms of femtosecond laser nanosurgery of cells and tissues,” Appl. Phys. B81(8), 1015–1047 (2005). [CrossRef]
  18. U. K. Tirlapur, K. König, C. Peuckert, R. Krieg, and K. J. Halbhuber, “Femtosecond near-infrared laser pulses elicit generation of reactive oxygen species in mammalian cells leading to apoptosis-like death,” Exp. Cell Res.263(1), 88–97 (2001). [CrossRef] [PubMed]
  19. K. König, P. T. C. So, W. W. Mantulin, and E. Gratton, “Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes,” Opt. Lett.22(2), 135–136 (1997). [CrossRef] [PubMed]
  20. I. R. Piletic, T. E. Matthews, and W. S. Warren, “Probing near-infrared photorelaxation pathways in eumelanins and pheomelanins,” J. Phys. Chem. A114(43), 11483–11491 (2010). [CrossRef] [PubMed]
  21. R. Lazova and J. M. Pawelek, “Why do melanomas get so dark?” Exp. Dermatol.18(11), 934–938 (2009). [CrossRef] [PubMed]
  22. D. Débarre and E. Beaurepaire, “Quantitative characterization of biological liquids for third-harmonic generation microscopy,” Biophys. J.92(2), 603–612 (2007). [CrossRef] [PubMed]
  23. M. C. Fischer, H. C. Liu, I. R. Piletic, Y. Escobedo-Lozoya, R. Yasuda, and W. S. Warren, “Self-phase modulation signatures of neuronal activity,” Opt. Lett.33(3), 219–221 (2008). [CrossRef] [PubMed]
  24. H. S. Sakhalkar, M. Dewhirst, T. Oliver, Y. Cao, and M. Oldham, “Functional imaging in bulk tissue specimens using optical emission tomography: fluorescence preservation during optical clearing,” Phys. Med. Biol.52(8), 2035–2054 (2007). [CrossRef] [PubMed]
  25. A. Gnoli, L. Razzari, and M. Righini, “Z-scan measurements using high repetition rate lasers: how to manage thermal effects,” Opt. Express13(20), 7976–7981 (2005). [CrossRef] [PubMed]

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