Cross-phase modulation imaging

Abstract

We demonstrate a cross-phase modulation measurement technique based on the sensitive detection of modulation transfer in a pump-probe setup. By modulating the amplitude of the pump beam and spectrally analyzing the probe beam, we achieve a rapid, background-free measurement of nonlinear phase modulation using power levels acceptable in biological imaging. This measurement technique would allow the extension of widely employed phase microscopy methods to the nonlinear regime, providing intrinsic and universal nonlinear contrast for biological imaging.

Pump-probe nonlinear phase dispersion spectroscopy

“…This method has had a significant impact on both biomedical applications [1,2], particularly quantitative melanoma detection [3,4], and art conservation [5]. On the other hand, various techniques have been developed to provide contrast from nonpigmented samples by using nonlinear phase changes (e.g., self/cross phase modulation), which provide greater detail of a sample's morphology [6][7][8][9], but for the most part, lack molecular specificity. One exception is a modified pump-probe system that uses polarization effects to determine the diffusive motions of molecules based on the non-instantaneous components of the optical Kerr effect (i.e., nuclear response) [10].…”

Accumulating advantages, reducing limitations: Multimodal nonlinear imaging in biomedical sciences – The synergy of multiple contrast mechanisms

“…Hence, the in general lowest order nonlinear quantity in matter is c (3) or the second order hyperpolarizability g. Nonlinear effects described by this quantity include two photon absorption (TPA), two photon excited fluorescence (2PF), three photon excited fluorescence (3PF), third harmonic generation (THG), four wave mixing [19] (FWM) and multiple coherent Raman scattering (CRS) processes, e.g., stimulated Raman scattering [20], coherent antiStokes Raman scattering (CARS) [21], coherent Stokes Raman scattering (CSRS) and Raman induced Kerr effect (RIKE) [22]. Recently a variety of additional nonlinear contrast mechanisms has been proposed, e.g., cross phase modulation microscopy [23,24], or nonlinear phase dispersion microscopy [25]. The most important processes are schematically depicted in Figure 1.…”

“…As in interferometric SHG the phase of the emitted signal is also the source of contrast in crossphase modulation and related pump-probe microscopic techniques [23][24][25]38]. In general, methods based on pump-probe microscopy allow detecting the phase, amplitude, wavelength and time-delay to generate image contrast.…”

Femtosecond pulse shaping enables detection of optical Kerr-effect (OKE) dynamics for molecular imaging

“…Future work will focus on improving the imaging system’s sensitivity and speed by operating in reflection mode, descanning, and detecting the pulse train with a high-resolution spectrometer. The methods presented here bridge the gap between extremely sensitive methods that are too slow for imaging applications [14–16], and those that are well suited for imaging but lack the means to access the time-resolved OKE dynamics [9,11,21]. This novel form of molecular contrast could lead to exciting applications in cell biology and medicine.…”

“…To overcome these challenges Fischer and colleagues have developed a number of techniques based on femtosecond pulse shaping that measure n 2 with the same inherent cross-sectional capabilities as MPEF microscopy, at fast speeds and with high sensitivity [9–12]. These methods have been applied to, for example, monitoring chemically activated neurons [10] and imaging of various biological samples [11–13]. However, these methods are mostly sensitive to the instantaneous nonresonant electronic response, which, unlike the other aforementioned nonlinear interactions, has poor molecular specificity.…”