Photothermal speckle modulation for noncontact materials characterization.

We have developed a noncontact, photothermal materials characterization method based on visible-light speckle imaging. This technique is applied to remotely measure the infrared absorption spectra of materials and to discriminate materials based on their thermal conductivities. A wavelength-tunable (7.

Coherent Raman tissue imaging in the brain.

Imaging in neuroscience has been dramatically impacted by the advent of multiphoton microscopy. Multiphoton-excited fluorescence (MPF) in combination with endogenous fluorophores or labeling by fluorescent molecules has proven to be particularly powerful. However, endogenous fluorescence is limited to relatively few molecular species, and practical labeling schemes do not exist for many classes of molecules.

Multicolored stain-free histopathology with coherent Raman imaging.

Conventional histopathology with hematoxylin & eosin (H&E) has been the gold standard for histopathological diagnosis of a wide range of diseases. However, it is not performed in vivo and requires thin tissue sections obtained after tissue biopsy, which carries risk, particularly in the central nervous system. Here we describe the development of an alternative, multicolored way to visualize tissue in real-time through the use of coherent Raman imaging (CRI), without the use of dyes.

Rational design and optimization of plasmonic nanoarrays for surface enhanced infrared spectroscopy.

We present an approach for rational design and optimization of plasmonic arrays for ultrasensitive surface enhanced infrared absorption (SEIRA) spectroscopy of specific protein analytes. Motivated by our previous work that demonstrated sub-attomole detection of surface-bound silk fibroin [Proc. Natl.

Coherent Raman scanning fiber endoscopy.

Coherent Raman scattering methods allow for label-free imaging of tissue with chemical contrast and high spatial and temporal resolution. However, their imaging depth in scattering tissue is limited to less than 1 mm, requiring the development of endoscopes to obtain images deep inside the body. Here, we describe a coherent Raman endoscope that provides stimulated Raman scattering images at seven frames per second using a miniaturized fiber scanner, a custom-designed objective lens, and an optimized scheme for collection of scattered light from the tissue.

Imaging drug delivery to skin with stimulated Raman scattering microscopy.

Efficient drug delivery to the skin is essential for the treatment of major dermatologic diseases, such as eczema, psoriasis and acne. However, many compounds penetrate the skin barrier poorly and require optimized formulations to ensure their bioavailability. Here, stimulated Raman scattering (SRS) microscopy, a recently developed, label-free chemical imaging tool, is used to acquire high resolution images of multiple chemical components of a topical formulation as it penetrates into mammalian skin.

Optical heterodyne-detected Raman-induced Kerr effect (OHD-RIKE) microscopy.

Label-free microscopy based on Raman scattering has been increasingly used in biomedical research to image samples that cannot be labeled or stained. Stimulated Raman scattering (SRS) microscopy allows signal amplification of the weak Raman signal for fast imaging speeds without introducing the nonresonant background and coherent image artifacts that are present in coherent anti-Stokes Raman scattering (CARS) microscopy. Here we present the Raman-induced Kerr effect (RIKE) as a contrast for label-free microscopy.

Label-free imaging of biomolecules in food products using stimulated Raman microscopy.

The development of methods that allow microscale studies of complex biomaterials based on their molecular composition is of great interest to a wide range of research fields. We show that stimulated Raman scattering (SRS) microscopy is an excellent analytical tool to study distributions of different biomolecules in multiphasic systems. SRS combines the label-free molecular specificity of vibrational spectroscopy with an enhanced sensitivity due to coherent excitation of molecular vibrations.

Label-free imaging of biomolecules in food products using stimulated Raman microscopy.

The development of methods that allow microscale studies of complex biomaterials based on their molecular composition is of great interest to a wide range of research fields. We show that stimulated Raman scattering (SRS) microscopy is an excellent analytical tool to study distributions of different biomolecules in multiphasic systems. SRS combines the label-free molecular specificity of vibrational spectroscopy with an enhanced sensitivity due to coherent excitation of molecular vibrations.

Synchronized time-lens source for coherent Raman scattering microscopy.

We use the time-lens concept to demonstrate a new scheme for synchronization of two pulsed light sources for biological imaging. An all fiber, 1064 nm time-lens source is synchronized to a picosecond solid-state Ti: Sapphire mode-locked laser by using the mode-locked laser pulses as the clock. We demonstrate the application of this synchronized source for CARS and SRS imaging by imaging mouse tissues.

Video-rate molecular imaging in vivo with stimulated Raman scattering.

Optical imaging in vivo with molecular specificity is important in biomedicine because of its high spatial resolution and sensitivity compared with magnetic resonance imaging. Stimulated Raman scattering (SRS) microscopy allows highly sensitive optical imaging based on vibrational spectroscopy without adding toxic or perturbative labels. However, SRS imaging in living animals and humans has not been feasible because light cannot be collected through thick tissues, and motion-blur arises from slow imaging based on backscattered light.

Intracavity wavelength modulation of an optical parametric oscillator for coherent Raman microscopy.

We present a novel intracavity frequency modulation scheme in a tunable, picosecond optical parametric oscillator (OPO). The OPO signal wavelength can be modulated with a depth of more than 10 nm at a rate of 38 MHz (one half its repetition rate). We discuss the design and construction of the light source and its application to the recently-developed frequency modulation coherent anti-Stokes Raman scattering (FM-CARS) and stimulated Raman scattering (SRS) techniques.

Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy.

Label-free chemical contrast is highly desirable in biomedical imaging. Spontaneous Raman microscopy provides specific vibrational signatures of chemical bonds, but is often hindered by low sensitivity. Here we report a three-dimensional multiphoton vibrational imaging technique based on stimulated Raman scattering (SRS).

Three-dimensional imaging of chemical bond orientation in liquid crystals by coherent anti- Stokes Raman scattering microscopy.

Liquid crystals are a class of industrially important materials whose optical properties make them useful particularly in display technology. Optical imaging of these materials provides information about their structure and physical properties. Coherent anti-Stokes Raman scattering (CARS) microscopy is used to provide three-dimensional chemical maps of liquid crystalline samples without the use of external labels.

CH-stretching overtone spectroscopy of 1,1,1,2-tetrafluoroethane.

We have recorded the vibrational absorption spectrum of 1,1,1,2-tetrafluoroethane (HFC-134a) in the fundamental and first five CH-stretching overtone regions with the use of Fourier transform infrared, dispersive long-path, intracavity laser photoacoustic, and cavity ringdown spectroscopies. We compare our measured total oscillator strengths in each region with intensities calculated using an anharmonic oscillator local mode model. We calculate intensities with 1D, 2D, and 3D Hamiltonians, including one or two CH stretches and two CH stretches with the HCH bending mode, respectively.

High-sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM CARS) microscopy.

We demonstrate a new approach to coherent anti-Stokes Raman scattering (CARS) microscopy that significantly increases the detection sensitivity. CARS signals are generated by collinearly overlapped, tightly focused, and raster scanned pump and Stokes laser beams, whose difference frequency is rapidly modulated. The resulting amplitude modulation of the CARS signal is detected through a lock-in amplifier.