Dvir Yelin

Laser scanning third-harmonic-generation microscopy in biology

A laser scanning microscope using third-harmonic generation as a probe is shown to produce high-resolution images of transparent biological specimens. Third harmonic light is generated by a tightly focused short-pulse laser beam and collected point-by-point to form a digital image. Demonstrations with two biological samples are presented. Live neurons in a cell culture are imaged with clear and detailed images, including organelles at the threshold of optical resolution. Internal organelles of yeast cells are also imaged, demonstrating the ability of the technique for cellular and intracellular imaging.

Adaptive femtosecond pulse compression

A practical adaptive method for femtosecond optical pulse compression is demonstrated experimentally for the first time to our knowledge. The method is robust and capable of handling the general case of pulse compression, in which the input pulses are completely uncharacterized or partially characterized.

Multiphoton plasmon-resonance microscopy

A novel method for detection of noble-metal nanoparticles by their nonlinear optical properties is presented and applied for specific labeling of cellular organelles. When illuminated by laser light in resonance with their plasmon frequency these nanoparticles generate an enhanced multiphoton signal. This enhanced signal is measured to obtain a depth-resolved image in a laser scanning microscope setup. Plasmon-resonance images of both live and fixed cells, showing specific labeling of cellular organelles and membranes, either by two-photon autofluorescence or by third-harmonic generation, are presented.

Double-clad fiber for endoscopy

Endoscopes employing a single optical fiber may have advantages over conventional fiber-bundle or CCD array imaging techniques, including the potential for greater flexibility and miniaturization. Although single-mode fibers can provide superior resolution compared with multimode fibers, they are prone to increased speckle noise and suffer from limited optical throughput and reduced depth of field. We demonstrate the use of a double-clad fiber for single-mode illumination and multimode detection to achieve high-resolution, reduced-speckle imaging with high optical throughput and a large depth of field.

Three-dimensional miniature endoscopy

A single optical fibre acts as a flexible probe to transmit a superior image of an internal landscape.The narrow viewMicroendoscopy, using devices a millimetre or so in diameter, is an accepted technique in ophthalmics, tumour diagnosis and other medical specialities. Submillimetre-diameter devices have been used in some clinical applications but have not been widely adopted because of their rigidity and poor image quality. A new type of endoscope has now been developed that can transmit video-rate, three-dimensional images from flexible probes that are the diameter of a single optical fibre, at 80–250 μm, comparable in size to a human hair.

Three-dimensional imaging using spectral encoding heterodyne interferometry

We present a novel heterodyne approach for performing fast, three-dimensional spectrally encoded imaging. Volumetric data of a volunteers finger and of coin surfaces were acquired at a rate of 5 volume sets per second with a depth resolution of 145 microm.

Adaptive real-time femtosecond pulse shaping

Experimental results of a practical self-learning pulse-shaping system are presented. Real-time adaptive pulse shaping of uncharacterized pulses is achieved. A cross-correlation feedback measurement of the output pulses is used by a simulated-annealing algorithm to modify the pulses iteratively toward target shapes. This scheme can readily be used for coherent control of quantum dynamics.

Real-time spatial–spectral interference measurements of ultrashort optical pulses

Real-time linear spectral interference measurements of ultrashort pulses are shown experimentally. The technique involves measurements of the two-dimensional interference pattern of the spectral interference between a reference and a signal pulse propagating at an angle with respect to each other. No postprocessing is needed to extract the spectral phase difference between the two pulses. Quadratic spectral phase distortions as well as spectral phase discontinuities are measured. The method is applicable to single-shot measurements of ultraweak pulses and is useful for identification of the critical adjustments of ultrashort pulse shapers and compressors.

High levels of reactive oxygen species in gold nanoparticle-targeted cancer cells following femtosecond pulse irradiation

Cancer cells could be locally damaged using specifically targeted gold nanoparticles and laser pulse irradiation, while maintaining minimum damage to nearby, particle-free tissue. Here, we show that in addition to the immediate photothermal cell damage, high concentrations of reactive oxygen species (ROS) are formed within the irradiated cells. Burkitt lymphoma B cells and epithelial breast cancer cells were targeted by antibody-coated gold nanospheres and irradiated by a few resonant femtosecond pulses, resulting in significant elevation of intracellular ROS which was characterized and quantified using time-lapse microscopy of different fluorescent markers. The results suggest that techniques that involve targeting of various malignancies using gold nanoparticles and ultrashort pulses may be more effective and versatile than previously anticipated, allowing diverse, highly specific set of tools for local cancer therapy.

Depth-resolved structural imaging by third-harmonic generation microscopy

Third harmonic generation microscopy is shown to be a robust method for obtaining structural information on a variety of biological specimens. Its nature allows depth-resolved imaging of inhomogeneities with virtually no background from surrounding homogeneous media. With an appropriate illumination geometry, third harmonic generation microscopy is shown to be particularly suitable for imaging of biogenic crystals, enabling extraction of the crystal orientation.