Nonlinear optical microscopy for drug delivery monitoring and cancer tissue imaging

A multimodal nonlinear optical microscope that combines coherent anti‐Stokes Raman scattering (CARS), two‐photon excitation fluorescence (TPEF), second‐harmonic generation (SHG) and sum‐frequency generation (SFG) was developed and applied to image breast cancer tissue and MCF‐7 cells as well as monitoring anticancer drug delivery in live cells. TPEF imaging showed that drugs are preferentially localized in the cytoplasm and the nuclear envelope in resistant cells. Moreover, the extracellular matrix was observed by TPEF signals arising from elastin's autofluorescence and SHG signals from collagen fibrils in breast tissue sections. Additionally, CARS signals arising from proteins and (PO₂)⁻ allowed identification of tumors. Label‐free imaging with chemical contrast of significant components of cancer cells and tissue suggests the potential of multimodal nonlinear optical microscopy for early detection and diagnosis of cancer. Copyright © 2010 John Wiley & Sons, Ltd.     

Two‐beam multiplexed CARS based on a broadband oscillator

A two‐beam multiplexed coherent anti‐Stokes Raman scattering (CARS) microscopy setup is demonstrated by using a broadband (BB) Ti:sapphire oscillator without using any specialty fibres. A well‐defined spectral structure of the source leads to a delay‐sensitive CARS measurement in two‐colour CARS and also provides an efficient means of obtaining three‐colour CARS signals combined with the dispersion compensation of the BB pulse. Our result implies that the background suppression is limited by the onset of the spurious signals caused by the different CARS process, qualitatively differing from what is typically observed in the CARS microscopy. Copyright © 2010 John Wiley & Sons, Ltd.     

基于光谱技术的Bipls算法结合CARS算法的苹果可溶性固形物含量检测

可溶性固形物含量是判断苹果内部品质的重要参考属性之一。利用高光谱技术获取苹果感兴趣区域的反射光谱,以S-G平滑(Savitzky-Golay smoothing)和直接正交信号校正(Direct orthogonal signal correction, DOSC)算法对光谱数据进行梯度预处理后,用后向区间偏最小二乘法(Bipls)优选出3,5,6,7,8,9,13,14,15,16,17,18,19,20,21,23等16个子区间,共计177个波长。结合竞争自适应重加权采样算法(CARS)再作进一步筛选,提取出449.6,512.9,544.8,547.2,594.3,596.8,928.2 nm等7个特征波长,利用偏最小二乘算法(PLS)建立基于特征波长的可溶性固形物含量检测模型,所得模型评价为R_c=0.906 2,RMSEC为0.482 2,R_p=0.871 6,RMSEP为0.614 0。该算法模型预测性能同Bipls和Bipls-SPA模型相比更为优异,证明了Bipls结合CARS算法在提高苹果可溶性固体物含量检测精度方面的有效性。     

Vibrational dynamics of nitromethane mixed with IR780 dye studied by coherent anti‐stokes Raman spectroscopy

Vibrational coupling between different kinds of molecules in liquid mixture is studied by multiplex coherent anti‐Stokes Raman spectroscopy (CARS). To identify vibrational coherence, fs‐probe with high time resolution and narrowband‐probe with high spectral resolution are adopted in CARS experiments. Using liquid nitromethane (NM) mixed with organic dye IR780 perchlorate as the sample, we can clearly observe the interference between different vibrational modes. The intermolecular vibrational interaction between NM and IR780 molecules results in the vibrational coherence transfer (VCT) in the form of a change of phase correlation. Compared with symmetric bending vibration of NO₂, coherence transfer is found to be easier to take place between C―N bond of NM and vibrations of IR780, which indicates the selectivity of intermolecular vibrational interaction. The selectivity is deduced to be related to the coordination between intramolecular and collective motion of molecules. Copyright © 2016 John Wiley & Sons, Ltd.     

Temperature and spatial diffusion of atoms cooled in a 3D lin ⊥lin bright optical lattice

We present a detailed experimental study of a three-dimensional lin⊥lin bright optical lattice. Measurements of the atomic temperature and spatial diffusion coefficients are reported for different angles between the lattice beams, i.e. for different lattice constants. The experimental findings are interpreted with the help of numerical simulations. In particular we show, both experimentally and theoretically, that the temperature is independent of the lattice constant. Received 5 July 2001 and Received in final form 13 August 2001     

Pump and probe nonlinear processes: new modified sum rules from a simple oscillator model

The nonlinear oscillator model is useful to basically understand the most important properties of nonlinear optical processes. It has been shown to give the correct asymptotic behaviour and to provide the general features of harmonic generation to all orders, in particular dispersion relations and sum rules. We investigate the properties of pump and probe processes using this model, and study those cases where general theorems based on the holomorphic character of the Kubo response functions cannot be applied. We show that it is possible to derive new sum rules and new Kramers-Kr?nig relations for the two lowest moments of the real and of the imaginary part of the third order susceptibility and that new specific contributions become relevant as the intensity of the probe increases. Since the analytic properties of the susceptibility functions depend only upon the time causality of the system we are confident that these results are not model dependent and therefore have a general validity, provided one substitutes for the equilibrium values of the potential derivatives the density matrix expectation values of the corresponding operators. Received 25 January 1999 and Received in final form 26 April 1999     

基于高光谱的鸡蛋新鲜度检测

借助高光谱成像仪采集贮期白壳鸡蛋的透射高光谱数据,对比测量常规表征新鲜度的哈夫单位值,用Matrix Laboratory (MATLAB)和Statistical Analysis System (SAS)等软件,同时结合化学计量法对样品鸡蛋的高光谱数据进行分析处理,建立了基于高光谱技术的鸡蛋新鲜度预测模型。选用高光谱500～1 000 nm的波段作为敏感波段进行研究,用马氏距离剔除鸡蛋异常样本数据,并对鸡蛋高光谱数据进行了微分校正,通过比较发现高光谱二阶微分与鸡蛋哈夫单位值之间的线性度高,因此选用高光谱二阶微分数据来进一步研究,并对其进行了小波去噪、光滑处理及标准化处理。选用近年新提出来的competitive adaptive reweighted sampling (CARS)变量选取法对高光谱进行降维,提取出32个特征参数,建立了白壳蛋基于全波段的偏最小二乘法(partial least square, PLS)预测模型和基于特征参数的多元回归模型,验证集的相关系数分别为0.88,0.93,均方误差分别为7.565,6.44。用验证集的蛋对基于高光谱二阶微分全波段的偏最小二乘法预测模型、基于特征参数的多元回归模型分别进行验证,两个模型判别白壳蛋新鲜和不新鲜的最高准确率达100%,88%。     

Selective excitation and suppression of coherent anti-Stokes Raman scattering by shaping femtosecond pulses

Femtosecond coherent anti-Stokes Raman scattering (CARS) suffers from poor selectivity between neighbouring Raman levels due to the large bandwidth of the femtosecond pulses. This paper provides a new method to realize the selective excitation and suppression of femtosecond CARS by manipulating both the probe and pump (or Stokes) spectra. These theoretical results indicate that the CARS signals between neighbouring Raman levels are differentiated from their indistinguishable femtosecond CARS spectra by tailoring the probe spectrum, and then their selective excitation and suppression can be realized by supplementally manipulating the pump (or Stokes) spectrum with the $\pi $ spectral phase step.     

Time‐resolved investigation of the ν1 ro‐vibrational Raman band of H2CO with fs‐CARS

The technique of femtosecond time‐resolved coherent anti‐Stokes scattering (fs‐CARS) is used to investigate the strongly perturbed ν₁ ro‐vibrational Raman band of formaldehyde (H₂CO). The time‐dependent signal is simulated using a ‘Watson‐’Hamiltonian in A‐type reduction and Raman theory for asymmetric rotors. The results are compared with the experimental data. The fs‐CARS method measures the evolution of the polarization in a molecular ensemble via superposition of many states and is sensitive to spectral irregularities or line shifts of the involved transitions. ‘Coriolis’ interactions play a major role in the analysis of the ν₁ band of formaldehyde. We successfully simulate the fs‐CARS transient signal from the ν₁ band of formaldehyde including a model for multiple ‘Coriolis’ interactions, without the necessity of describing the complete interaction between all the vibrational levels. ‘Coriolis’ coupling coefficients and energy shifts are derived from the experiment by a least‐square fit. The results are discussed and compared to literature values. Copyright © 2006 John Wiley & Sons, Ltd.     

Coherent anti-Stokes Raman scattering microscopy for polymers

Coherent anti-stokes Raman scattering (CARS) microscopy is a label-free chemical imaging modality capable of interrogating local molecular composition, concentration, and even orientation. In comparison to traditional Raman spectroscopy/imaging, CARS generates signals that are typically orders-of-magnitude stronger, enabling high-throughput and large-area imaging with superior spectroscopic fidelity. In this review, we present an overview of CARS microscopy as applied to polymer science, covering such timely and important topics as drug release and reaction kinetics to 3D molecular structures and orientation. We also discuss outstanding opportunities and challenges to using CARS microscopy as a quantitative measurement method.