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Optics Express

Optics Express

  • Editor: C. Martijn de Sterke
  • Vol. 20, Iss. 4 — Feb. 13, 2012
  • pp: 4484–4493
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All-fiber laser source for CARS microscopy based on fiber optical parametric frequency conversion

Martin Baumgartl, Mario Chemnitz, Cesar Jauregui, Tobias Meyer, Benjamin Dietzek, Jürgen Popp, Jens Limpert, and Andreas Tünnermann  »View Author Affiliations


Optics Express, Vol. 20, Issue 4, pp. 4484-4493 (2012)
http://dx.doi.org/10.1364/OE.20.004484


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Abstract

A novel approach for an all-fiber mono-laser source for CARS microscopy is presented. An Yb-fiber laser generates 100 ps pulses, which later undergo narrowband in-fiber frequency conversion based on degenerate four-wave-mixing. The frequency conversion is optimized to access frequency shifts between 900 and 3200cm−1, relevant for vibrational imaging. Inherently synchronized pump and Stokes pulses are available at one fiber end, readily overlapped in space and time. The source is applied to CARS spectroscopy and microscopy experiments in the CH-stretching region around 3000cm−1. Due to its simplicity and maintenance-free operation, the laser scheme holds great potential for bio-medical applications outside laser laboratories.

© 2012 OSA

1. Introduction

Coherent anti-Stokes Raman scattering (CARS) microscopy has proven to be a powerful tool in biomedical sciences [1

1. C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif) 1(1), 883–909 (2008). [CrossRef] [PubMed]

]. By probing intrinsic vibrational molecule resonances of the specimen, chemical selective image contrast is obtained without the use of extrinsic labels [2

2. A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999). [CrossRef]

]. Paired with its high sensitivity, CARS thus allows for microscopy of living cells and is a promising technique for real time in-vivo imaging, e.g. during brain cancer surgery.

As CARS is a four-wave-mixing (FWM) process, the signal generation requires synchronized laser pulses at different wavelengths. This imposes stringent requirements on the light source. At the same time, the frequency difference between the two synchronized pulse trains needs to match the molecular resonance of interest to obtain the desired chemical-selective contrast through the generation of a resonant anti-Stokes signal. Since the signal intensity is proportional to the pump/probe and Stokes intensities ICARS~I2pIs, signal photons are primarily generated in a small focal volume, thus CARS additionally provides 3-dimensional sectioning capabilities.

The common approach to generate the pump and Stokes pulses is to use two synchronized mode-locked solid state lasers or one mode-locked laser in combination with an optical parametric oscillator (OPO), the latter approach thereby obviating the need for electronic synchronization. These systems are very versatile and deliver nearly ideal parameters. On the other hand, they are very expensive, large and require technical staff devoted to their constant alignment and maintenance. For this reason the application of CARS microscopy is still limited to a few specialized laboratories world-wide. A wider use in life sciences and especially in clinical environments critically depends on the development of suitable, easy-to-use, compact and, at the same time, inexpensive and reliable laser sources.

Fiber lasers are ideally suited to fulfill all these requirements, as they can be completely fiber integrated and, therefore, they can be extremely compact and robust. Hence, several sources intended for CARS microscopy have been developed using a fiber based driving laser in combination with some sort of frequency conversion process for the intrinsically synchronized generation of the frequency shifted pulse train. Different approaches for frequency conversion relying either on bulk crystal based OPO [3

3. K. Kieu, B. G. Saar, G. R. Holtom, X. S. Xie, and F. W. Wise, “High-power picosecond fiber source for coherent Raman microscopy,” Opt. Lett. 34(13), 2051–2053 (2009). [CrossRef] [PubMed]

] or fiber based processes such as soliton self-frequency shift (SSFS) [4

4. E. R. Andresen, C. K. Nielsen, J. Thøgersen, and S. R. Keiding, “Fiber laser-based light source for coherent anti-Stokes Raman scattering microspectroscopy,” Opt. Express 15(8), 4848–4856 (2007). [CrossRef] [PubMed]

,5

5. A. F. Pegoraro, A. Ridsdale, D. J. Moffatt, J. P. Pezacki, B. K. Thomas, L. Fu, L. Dong, M. E. Fermann, and A. Stolow, “All-fiber CARS microscopy of live cells,” Opt. Express 17(23), 20700–20706 (2009). [CrossRef] [PubMed]

] or supercontinuum generation (SC) [6

6. M. Marangoni, A. Gambetta, C. Manzoni, V. Kumar, R. Ramponi, and G. Cerullo, “Fiber-format CARS spectroscopy by spectral compression of femtosecond pulses from a single laser oscillator,” Opt. Lett. 34(21), 3262–3264 (2009). [CrossRef] [PubMed]

] have been pursued. Whereas a bulk OPO is clearly not compatible with fiber integration, also the fiber based approaches rely on free-space optics to some extent. One problem is that the frequency shifted solitons tend to be spectrally broad and, hence, they must be adapted to obtain high spectral resolution and a high contrast between the resonance and the non-resonant background in the CARS signal [1

1. C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif) 1(1), 883–909 (2008). [CrossRef] [PubMed]

]. Furthermore, it is beneficial for the frequency conversion process (SSFS, SC) if the driving laser pulse is in the fs time scale [7

7. K. L. Corwin, N. R. Newbury, J. M. Dudley, S. Coen, S. A. Diddams, K. Weber, and R. S. Windeler, “Fundamental noise limitations to supercontinuum generation in microstructure fiber,” Phys. Rev. Lett. 90(11), 113904 (2003). [CrossRef] [PubMed]

], whereas for CARS mostly ps pulses are preferable. One strategy to solve this issue is to start with a narrowband ps driving laser and convert part of its output to fs durations before it is sent to the frequency conversion stage [4

4. E. R. Andresen, C. K. Nielsen, J. Thøgersen, and S. R. Keiding, “Fiber laser-based light source for coherent anti-Stokes Raman scattering microspectroscopy,” Opt. Express 15(8), 4848–4856 (2007). [CrossRef] [PubMed]

]. This is done by exploiting nonlinear spectral broadening in a fiber and by carrying out a subsequent temporal compression in a grating setup. Other approaches directly start with fs pulses and use second harmonic generation in long crystals to achieve spectral pulse compression at the end [6

6. M. Marangoni, A. Gambetta, C. Manzoni, V. Kumar, R. Ramponi, and G. Cerullo, “Fiber-format CARS spectroscopy by spectral compression of femtosecond pulses from a single laser oscillator,” Opt. Lett. 34(21), 3262–3264 (2009). [CrossRef] [PubMed]

], or alternatively, they apply a spectrally focused CARS scheme by chirping the broadband pulses [5

5. A. F. Pegoraro, A. Ridsdale, D. J. Moffatt, J. P. Pezacki, B. K. Thomas, L. Fu, L. Dong, M. E. Fermann, and A. Stolow, “All-fiber CARS microscopy of live cells,” Opt. Express 17(23), 20700–20706 (2009). [CrossRef] [PubMed]

]. Also more sophisticated techniques like delayed multiplex CARS with ultrabroadband few cycle pulses have been demonstrated [8

8. R. Selm, M. Winterhalder, A. Zumbusch, G. Krauss, T. Hanke, A. Sell, and A. Leitenstorfer, “Ultrabroadband background-free coherent anti-Stokes Raman scattering microscopy based on a compact Er:fiber laser system,” Opt. Lett. 35(19), 3282–3284 (2010). [CrossRef] [PubMed]

]. However, despite considerable progress, none of the presented concepts offers true turn-key and alignment-free operation as they depend on free-space optics and need adjustment of the pulse delay.

In this paper, we present a novel approach for all-fiber CARS laser sources which allows for complete fiber integration. Our system comprises a spectrally filtered fiber oscillator and a fiber optical parametric frequency conversion stage using degenerate four-wave-mixing (FWM) in an endlessly single-mode fiber. The frequency shift that can be obtained is determined by the fiber dispersion, which in turn influences the phase-matching condition of the parametric process. Moreover this frequency shift can be changed by tuning the wavelength of the driving fiber laser. Furthermore the FWM process inherently ensures that the pump laser pulse and the shifted component are both temporally and spatially overlapped at the fiber output. Thus they are readily available for injection into a CARS microscope without the need of any combining optics or delay lines. This reduces overall system complexity significantly and makes it particularly easy to use. Besides, the single-fiber-end output is directly compatible with fiber-delivered probes [9

9. M. Balu, G. Liu, Z. Chen, B. J. Tromberg, and E. O. Potma, “Fiber delivered probe for efficient CARS imaging of tissues,” Opt. Express 18(3), 2380–2388 (2010). [CrossRef] [PubMed]

] for in-vivo imaging. This holds true, since long ps pulses have been used, for which the additional dispersion within the microscopic objective and the tissue sample and even within another short piece of delivery fiber is negligible.

Our experimental scheme is based on an alignment-free ytterbium fiber laser delivering 118 ps pulses at an average power of up to 2 W and with variable repetition rates in the lower MHz range. The FWM fiber was chosen to attain frequency shifts from more than 3500 cm−1 to below 1000 cm−1 by tuning the driving laser by +/−20nm within the Yb-gain bandwidth. In the following sections the pump laser (section 2) and the frequency conversion stage (section 3) will be described. Afterwards experimental results from CARS spectroscopy of the aromatic CH-stretching vibration of toluene and CARS microscopic images are presented in section 4.

2. The all-fiber pump laser system

To drive the nonlinear frequency conversion process, a reliable high-power pump laser is required. Hence, a fiber master oscillator power amplifier (MOPA) system, completely based on commercially available single-mode fiber components was developed. The exclusive use of polarization maintaining fibers results in an environmentally stable system. Furthermore, all components in the setup are fusion spliced to obtain alignment-free operation.

3. In-fiber frequency conversion by degenerate four-wave-mixing

The wavelength range from 780 to 980 nm for pumping the CARS process is beneficial for microscopy applications as it provides a good trade-off in terms of spatial resolution, penetration depth, non-resonant background and photodamage [1

1. C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif) 1(1), 883–909 (2008). [CrossRef] [PubMed]

]. This wavelength range is therefore, the most widely used. The corresponding Stokes wavelength is, consequently, above 1000 nm. In our case, in order to exploit the advantages of Yb-fiber laser technology, the Stokes wavelength is designed to fall within the Yb-gain bandwidth between 1020 and 1080 nm. The all-fiber single-laser approach pursued here requires then, the frequency conversion of this Stokes wavelength to shorter wavelengths. The frequency-converted signal should be strong enough to pump the CARS process. It has been shown that degenerate FWM in photonic-crystal fibers can generate distinct new frequencies with high spectral densities [11

11. W. Wadsworth, N. Joly, J. Knight, T. Birks, F. Biancalana, and P. Russell, “Supercontinuum and four-wave mixing with Q-switched pulses in endlessly single-mode photonic crystal fibres,” Opt. Express 12(2), 299–309 (2004). [CrossRef] [PubMed]

13

13. L. Lavoute, J. C. Knight, P. Dupriez, and W. J. Wadsworth, “High power red and near-IR generation using four wave mixing in all integrated fibre laser systems,” Opt. Express 18(15), 16193–16205 (2010). [CrossRef] [PubMed]

]. Endlessly single-mode PCF designs allow for high conversion efficiencies as they ensure a good mode overlap even for widely separated wavelengths. The use of long picosecond pulses minimizes spectral broadening of the driving pulses induced by self-phase modulation (SPM) and thus allows for narrowband signal generation.

In degenerate FWM two pump photons are annihilated and one signal and one idler photon are generated at shorter and longer wavelengths, respectively. To avoid confusion, the terms pump and signal are written in italic in the following, wherever they refer to the FWM process. This should distinguish them from the pump and signal of the CARS process. (Note that the signal generated by FWM will be used as the pump for the CARS process. Moreover, the residual FWM pump pulse will serve as the CARS Stokes (see upper inset Fig. 4). The parametric process of FWM can only take place if both energy pump=ωsignal+ωidler and momentum conservation 2kpump= ksignal+ kidler + 2γPpump are fulfilled [14

14. G. P. Agrawal, Nonlinear Fiber Optics (Academic, 2001).

]. The simultaneous fulfillment of these two conditions is known as phase-matching. Besides the product of nonlinearity parameter γ and pump power, the phase matching is only dependent on the dispersion of the fiber. Hence, the signal wavelength for a given pump can be conveniently selected by adjusting the structure parameters of the fiber. To select a suitable fiber we calculated the dispersion of the effective refractive index for different available PCFs (see legend in Fig. 3
Fig. 3 (a) DFWM frequency shift with respect to pump calculated for different PCF designs. The legend contains the geometrical parameters Λ (hole-to-hole distance) and d (hole diameter). (b) Microscope image of PCF#5. The legend provides the geometrical parameters of the different fibers. All fibers are standard one-hole-missing designs with hexagonal hole arrangement. Note, that the relative dimensions are the same for PCF#1-5, hence, suppressing the scale bar, the microscope image would be identical for PCF#1-5.
) using a numerical mode solver. Together with the equations above, the phase matched wavelength sets are easily determined for each fiber. Figure 4
Fig. 4 Signal and idler wavelengths that fulfill both energy and momentum conservation as a function of the pump wavelength, calculated for a peak power of 2 kW for PCF#2. The green curve shows the corresponding frequency shift with respect to the pump that is obtained for different pump wavelengths. The inset on the left shows the simulated mode profile at 1030nm, the upper inset illustrates the use of the different frequencies for CARS.
displays the calculated mode profile for PCF#2 and the corresponding signal (orange) and idler (black) wavelength pairs for pump wavelengths between 1 and 1.1 μm. Additionally, the frequency difference (green) between signal and pump is plotted. This shows whether the generated signal could be used together with the pump laser to drive any CARS resonance of interest. In fact, for PCF#2 tuning the pump between 1022 and 1055 nm generates the desired signal wavelengths between 770 and 964 nm. This corresponds to frequency shifts between 3200 and 900 cm−1. Thus tuning the pump by only 33 nm gives access to the whole frequency range important for CARS microscopy. Of course, the same frequency difference is obtained with the idler, which could alternatively be used whenever longer wavelengths are of interest.

The investigated PCFs are one-hole-missing designs consisting of 7 rings of air holes. A microscope image of the fiber cross section is shown in Fig. 3(b), the design parameters (hole-to-hole distance and size) are given in the legend. The simulated frequency shifts obtained for the different fibers assuming an Yb-doped pump laser are shown in Fig. 3(a). At fixed pump wavelength of 1030 nm, the frequency shifts span from 1528 to 4340 cm−1 with the presented fiber set, demonstrating the flexibility of the DFWM approach. We decided to use PCF#2 for our CARS experiments as it shifts across the important CH-stretching bands around 3000 cm−1 when using the pump laser around 1030 nm. Furthermore, as discussed above, this fiber perfectly maps the CARS relevant frequency range into a tuning range easily accessible with Yb-fiber lasers. The fiber’s mode-field area is around 14 μm2, which gives rise to sufficiently high intensities already at moderate peak powers of some kW. For comparison, the corresponding curve for a commercially available fiber (LMA-5 NKT Photonics) is plotted (gray). It shows nearly the same characteristic and, thus, it could readily be used for the development of a low cost commercial CARS laser source.

In reference [12

12. D. Nodop, C. Jauregui, D. Schimpf, J. Limpert, and A. Tünnermann, “Efficient high-power generation of visible and mid-infrared light by degenerate four-wave-mixing in a large-mode-area photonic-crystal fiber,” Opt. Lett. 34(22), 3499–3501 (2009). [CrossRef] [PubMed]

] it has been shown that the temporal pulse shape gets increasingly complex due to the occurrence of successive back-conversion processes in longer fiber sections. On the other hand, using a short conversion fiber, clean signal pulses can be generated, at the price of sacrificing some conversion efficiency. These signal pulses can be significantly shorter than the pump pulses, as conversion starts only around the pulse peak. As we are interested in clean signal generation, we chose such a working point. The temporal trace of the signal recorded with a photodiode (18.5 ps) and a sampling oscilloscope (70 GHz) is shown in Fig. 6(b)
Fig. 6 (a) Variation of the frequency shift by tuning the pump laser. (b) Temporal pulse shapes measured with a fast photo diode (18.5ps) and a sampling oscilloscope (70GHz). The FWM pump (gray), the FWM signal which is used as CARS pump (orange), and the residual, partially depleted FWM pump which is used as CARS Stokes (red) are shown. The area is normalized to the pulse energy to estimate the peak power.
. It has a full width at half maximum of 43 ps, which is about 3 times shorter than that of the pump pulse. More important, however, is the spectral width of the generated signal, as it influences the signal to noise ratio of the CARS signal due to the nonresonant background [1

1. C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif) 1(1), 883–909 (2008). [CrossRef] [PubMed]

]. Figure 5(b) shows the signal spectrum for different signal powers (obtained by increasing the pump power). With increasing power the spectral power density increases up to 15 mW/nm for 48 mW total signal power. However, as the signal width gets broader, the power density does not increase further when going to higher power. For our CARS experiments we worked with 20 to 35 mW frequency converted power. If higher power would be required, one would have to use higher repetition rates or shorter conversion fiber lengths to remain in the narrow linewidth operation point.

As mentioned above, by tuning the wavelength of the pump laser the frequency shift can be varied over a large range, whereby both pump and signal wavelengths change. A continuous tunability over a few nanometers can be obtained from our pump laser by stretching the FBG. The resulting FWM signal spectra in terms of frequency shift are shown in Fig. 6(a) for PCF#2. The signal wavelength changes from 775 to 788 nm when the pump is tuned from 1030.5 to 1033.5 nm. So the frequency shift changes by ~200 cm−1 with this 3 nm pump tuning.

4. Application of the two-color fiber source to CARS spectroscopy and microscopy

To demonstrate the suitability of the above concept for CARS applications, we performed a measurement of the aromatic CH-stretching vibrational resonance of toluene, using the simple scheme depicted in Fig. 7
Fig. 7 Simple CARS setup. The PCF output is simply collimated and focused into the sample. No additional delay line is required as the pulses are already overlapped. LP 650 - long pass 650nm, SP 770 - short pass 770nm, MMF - multi-mode fiber.
. After the pump laser being frequency shifted by DFWM in PCF#2, the output of the PCF is simply collimated and focused into the sample. No additional delay line is required as the pulses already overlap in space and time at the output of the fiber, which simplifies both the setup and the experimental effort, something of particular interest for the user. Behind the sample, the light is collected by a lens and coupled into a multimode fiber, which is connected to the detector. A 770nm short pass filter is inserted behind the sample to block any residual pump light. Another long pass filter (650nm) is used in front of the sample to block any small amount of light that might be present at the CARS signal wavelength, generated by non-phase-matched FWM in the PCF [9

9. M. Balu, G. Liu, Z. Chen, B. J. Tromberg, and E. O. Potma, “Fiber delivered probe for efficient CARS imaging of tissues,” Opt. Express 18(3), 2380–2388 (2010). [CrossRef] [PubMed]

].

About 26 mW of CARS pump is sent to a 10x microscope objective (Olympus) to be focused into the sample. The signal is detected with a CCD spectrometer, but it could of course be obtained by any non-spectrally sensitive detector as well. As the signal is strong, no special care had to be taken regarding efficient photon collection or stray light. Figure 8(a)
Fig. 8 (a) CARS signal spectra and (b) CARS signal power, obtained by tuning the pump-Stokes frequency shift across the resonance of toluene.
shows the CARS signal spectra for different frequency shifts between pump and Stokes. The width of each single spectrum is about 50 cm−1. Integration yields the total signal power, which is plotted in Fig. 8(b) together with a fit of the resonance line. The resulting linewidth is 60 cm−1 as a result of the convolution of the laser linewidth with the resonance.

In order to test the imaging capabilities of the laser source, we attached it to a home-built laser scanning microscope. Using a 20x objective (Mitutoyo Plan Apo NIR), images of glass spheres in toluene were taken (Fig. 9
Fig. 9 CARS microscope images of glass spheres in toluene, 970x970 pixels, no average. Detuning from resonance demonstrates high signal to noise ratios.
). Tuning to the resonance (left hand side of Fig. 9) the surrounding toluene generates a strong resonant CARS signal and hence appears bright, whereas the glass spheres remain dark creating a strong contrast in the picture. The raw images in Fig. 9 contain 970x970 pixels and were acquired in less than 2 seconds without averaging. The series in Fig. 9 shows how the signal vanishes when the laser is tuned out of resonance. The nonresonant background is in comparison to the resonant CARS signal almost negligible (compare Fig. 9 left-right).

Against the common notion that pulses in the short ps range are optimal for CARS, longer pulses in the range of tens of picoseconds have many practical advantages. Obviously the temporal overlap between pulses becomes much less critical and, thus, passing several optical elements or even a certain fiber segment does not require for any readjustments. Moreover, very narrow bandwidths and high spectral resolution is obtained for transform limited pulses at durations of several tens of ps, which, at the same time results in higher signal to noise ratios as the nonresonant background coming from besides the excited vibrational line is suppressed. Finally, and even more important, when it comes to fiber delivered probes, the impact of undesired propagation effects is drastically reduced. This relates to both dispersion and self-phase-modulation, when comparing pulses with equal peak power. At the same time longer pulses generate the same amount of CARS signal compared to shorter ones, as long as the peak and average power are kept constant. This implies that the product of the repetition rate and the pulse duration remains constant as illustrated in Fig. 10
Fig. 10 Illustration showing that long pulses (case B) yield the same CARS signal power as shorter ones (case A), as long as the repetition rate is lowered accordingly, keeping both average and peak power constant.
. Thus, when the pulse duration is increased, the pulse energy needs to be increased by the same factor to keep the peak power constant. In order to remain at the same average power, consequently, the repetition rate has to be decreased by that factor. This increase in pulse energy is inherently happening in the amplifier if the repetition rate is decreased. Under this prerequisite, each long pulse generates more CARS signal even though the total CARS average power remains constant. Hence, integration over several pulses for each pixel is not required anymore. On the other hand, fast acquisition times and real-time imaging require high repetition rates, thus repetition rates around few MHz represent a good trade-off. For example, a 1-MHz system would allow for an image of 300x300pixels at 11 frames per second.

5. Conclusion

We have demonstrated a novel all-fiber laser source approach for CARS microscopy based on degenerate FWM. An environmentally stable Yb-fiber laser generates 118 ps pulses around 1030 nm, which are then frequency converted in a PCF to obtain high-power, inherently synchronized CARS pump pulses with a duration of 43 ps. The generated wavelength pair around 780 nm and 1030 nm was used to probe the aromatic CH-stretch vibrational resonance of toluene at 3050 cm−1. Reproduction of the CARS resonance bandshape by spectral tuning as well as microscopic imaging within the aromatic CH-stretching region demonstrates the CARS capabilities of the laser.

In contrast to other fiber based frequency conversion arrangements on the basis of supercontinuum generation or Raman scattering based soliton shifts, FWM gives the opportunity for narrowband frequency conversion directly to shorter wavelengths. Using the emission of an Yb-fiber laser as CARS Stokes and as the field driving the FWM process, high-power CARS pump pulses can be generated in the preferred wavelength region around 800 nm. Alternatively the FWM idler around 1500 nm could be used as Stokes, whenever longer wavelengths would be required. Furthermore the FWM process is driven by long ps pulses and is consequently directly compatible with CARS, without the need for pulse post-processing like in other fs-based frequency conversion schemes.

The laser operates in the near infrared wavelength range offering several advantages as a maximized depth penetration and minimal sample absorption and photo damage in biological tissue. The long ps pulses minimize the influence of dispersion and do not loose temporal overlap. Furthermore the spectral resolution of the source with an excitation bandwidth of ~26 cm−1 as demonstrated corresponds to the linewidth of a vibrational resonance in the CH-stretching region (~20cm−1) for imaging lipids, thus, yielding a high ratio of resonant signal to nonresonant background. The resolution could be further improved by cw-seeding of the FWM process [15

15. P. J. Mosley, S. A. Bateman, L. Lavoute, and W. J. Wadsworth, “Low-noise, high-brightness, tunable source of picosecond pulsed light in the near-infrared and visible,” Opt. Express 19(25), 25337–25345 (2011). [CrossRef]

], which would condense the bandwidth closer to the transform limit. This would reduce the bandwidth to few cm−1.

The main advantage of the proposed approach, however, is its simplicity of operation due to its full fiber integration. It provides pump and Stokes pulses temporally and spatially overlapped from one fiber end in combination with a compact and maintenance-free overall system. Hence, it paves the way to fiber-delivered in situ imaging systems.

By replacing the fs- by a ps-oscillator with low repetition rate the system could be simplified even further. Only one core pumped main amplifier would be required which could be directly spliced between the oscillator and the conversion PCF. Also a high repetition rate fiber coupled microchip laser [16

16. A. Steinmetz, D. Nodop, A. Martin, J. Limpert, and A. Tünnermann, “Reduction of timing jitter in passively Q-switched microchip lasers using self-injection seeding,” Opt. Lett. 35(17), 2885–2887 (2010). [CrossRef] [PubMed]

] might be an alternative. With the whole system fitting into a small box, it could directly be attached to the microscope, thus becoming as easy to use as any halogen lamp. It could be made tunable by tuning the oscillator, but it could also be designed with a fixed frequency difference to serve one specific application as e.g. the imaging of lipids. As such, it could be a simple extension to existing fluorescence microscopes or a compact and reliable device for in situ imaging, thus being a significant step towards establishing CARS microscopy in real-world and, in particular, in bio-medical applications.

Acknowledgments

This work was partly supported by the German Federal Ministry of Education and Research (BMBF) under contract 13N10773 and 13N10774 as well as the Inter Carnot & Fraunhofer program under the project APUS. M. Baumgartl acknowledges support from the Carl-Zeiss-Stiftung. The authors thank T. V. Andersen from NKT Photonics for providing the photonic-crystal fibers.

References and links

1.

C. L. Evans and X. S. Xie, “Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu Rev Anal Chem (Palo Alto Calif) 1(1), 883–909 (2008). [CrossRef] [PubMed]

2.

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering,” Phys. Rev. Lett. 82(20), 4142–4145 (1999). [CrossRef]

3.

K. Kieu, B. G. Saar, G. R. Holtom, X. S. Xie, and F. W. Wise, “High-power picosecond fiber source for coherent Raman microscopy,” Opt. Lett. 34(13), 2051–2053 (2009). [CrossRef] [PubMed]

4.

E. R. Andresen, C. K. Nielsen, J. Thøgersen, and S. R. Keiding, “Fiber laser-based light source for coherent anti-Stokes Raman scattering microspectroscopy,” Opt. Express 15(8), 4848–4856 (2007). [CrossRef] [PubMed]

5.

A. F. Pegoraro, A. Ridsdale, D. J. Moffatt, J. P. Pezacki, B. K. Thomas, L. Fu, L. Dong, M. E. Fermann, and A. Stolow, “All-fiber CARS microscopy of live cells,” Opt. Express 17(23), 20700–20706 (2009). [CrossRef] [PubMed]

6.

M. Marangoni, A. Gambetta, C. Manzoni, V. Kumar, R. Ramponi, and G. Cerullo, “Fiber-format CARS spectroscopy by spectral compression of femtosecond pulses from a single laser oscillator,” Opt. Lett. 34(21), 3262–3264 (2009). [CrossRef] [PubMed]

7.

K. L. Corwin, N. R. Newbury, J. M. Dudley, S. Coen, S. A. Diddams, K. Weber, and R. S. Windeler, “Fundamental noise limitations to supercontinuum generation in microstructure fiber,” Phys. Rev. Lett. 90(11), 113904 (2003). [CrossRef] [PubMed]

8.

R. Selm, M. Winterhalder, A. Zumbusch, G. Krauss, T. Hanke, A. Sell, and A. Leitenstorfer, “Ultrabroadband background-free coherent anti-Stokes Raman scattering microscopy based on a compact Er:fiber laser system,” Opt. Lett. 35(19), 3282–3284 (2010). [CrossRef] [PubMed]

9.

M. Balu, G. Liu, Z. Chen, B. J. Tromberg, and E. O. Potma, “Fiber delivered probe for efficient CARS imaging of tissues,” Opt. Express 18(3), 2380–2388 (2010). [CrossRef] [PubMed]

10.

B. Ortaς, M. Plötner, T. Schreiber, J. Limpert, and A. Tünnermann, “Experimental and numerical study of pulse dynamics in positive net-cavity dispersion modelocked Yb-doped fiber lasers,” Opt. Express 15, 15595–15602 (2007).

11.

W. Wadsworth, N. Joly, J. Knight, T. Birks, F. Biancalana, and P. Russell, “Supercontinuum and four-wave mixing with Q-switched pulses in endlessly single-mode photonic crystal fibres,” Opt. Express 12(2), 299–309 (2004). [CrossRef] [PubMed]

12.

D. Nodop, C. Jauregui, D. Schimpf, J. Limpert, and A. Tünnermann, “Efficient high-power generation of visible and mid-infrared light by degenerate four-wave-mixing in a large-mode-area photonic-crystal fiber,” Opt. Lett. 34(22), 3499–3501 (2009). [CrossRef] [PubMed]

13.

L. Lavoute, J. C. Knight, P. Dupriez, and W. J. Wadsworth, “High power red and near-IR generation using four wave mixing in all integrated fibre laser systems,” Opt. Express 18(15), 16193–16205 (2010). [CrossRef] [PubMed]

14.

G. P. Agrawal, Nonlinear Fiber Optics (Academic, 2001).

15.

P. J. Mosley, S. A. Bateman, L. Lavoute, and W. J. Wadsworth, “Low-noise, high-brightness, tunable source of picosecond pulsed light in the near-infrared and visible,” Opt. Express 19(25), 25337–25345 (2011). [CrossRef]

16.

A. Steinmetz, D. Nodop, A. Martin, J. Limpert, and A. Tünnermann, “Reduction of timing jitter in passively Q-switched microchip lasers using self-injection seeding,” Opt. Lett. 35(17), 2885–2887 (2010). [CrossRef] [PubMed]

OCIS Codes
(060.4370) Fiber optics and optical communications : Nonlinear optics, fibers
(140.7300) Lasers and laser optics : Visible lasers
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(190.4370) Nonlinear optics : Nonlinear optics, fibers
(190.4380) Nonlinear optics : Nonlinear optics, four-wave mixing
(300.6230) Spectroscopy : Spectroscopy, coherent anti-Stokes Raman scattering
(180.4315) Microscopy : Nonlinear microscopy

ToC Category:
Lasers and Laser Optics

History
Original Manuscript: December 7, 2011
Revised Manuscript: January 18, 2012
Manuscript Accepted: January 18, 2012
Published: February 8, 2012

Virtual Issues
Vol. 7, Iss. 4 Virtual Journal for Biomedical Optics

Citation
Martin Baumgartl, Mario Chemnitz, Cesar Jauregui, Tobias Meyer, Benjamin Dietzek, Jürgen Popp, Jens Limpert, and Andreas Tünnermann, "All-fiber laser source for CARS microscopy based on fiber optical parametric frequency conversion," Opt. Express 20, 4484-4493 (2012)
http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-20-4-4484


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References

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  11. W. Wadsworth, N. Joly, J. Knight, T. Birks, F. Biancalana, and P. Russell, “Supercontinuum and four-wave mixing with Q-switched pulses in endlessly single-mode photonic crystal fibres,” Opt. Express12(2), 299–309 (2004). [CrossRef] [PubMed]
  12. D. Nodop, C. Jauregui, D. Schimpf, J. Limpert, and A. Tünnermann, “Efficient high-power generation of visible and mid-infrared light by degenerate four-wave-mixing in a large-mode-area photonic-crystal fiber,” Opt. Lett.34(22), 3499–3501 (2009). [CrossRef] [PubMed]
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  16. A. Steinmetz, D. Nodop, A. Martin, J. Limpert, and A. Tünnermann, “Reduction of timing jitter in passively Q-switched microchip lasers using self-injection seeding,” Opt. Lett.35(17), 2885–2887 (2010). [CrossRef] [PubMed]

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