3D laser nano-printing on fibre paves the way for super-focusing of multimode laser radiation.

Multimode high-power laser diodes suffer from inefficient beam focusing, leading to a focal spot 10-100 times greater than the diffraction limit. This inevitably restricts their wider use in 'direct-diode' applications in materials processing and biomedical photonics. We report here a 'super-focusing' characteristic for laser diodes, where the exploitation of self-interference of modes enables a significant reduction of the focal spot size. This is achieved by employing a conical microlens fabricated on the tip of a multimode optical fibre using 3D laser nano-printing (also known as multi-photon lithography). When refracted by the conical surface, the modes of the fibre-coupled laser beam self-interfere and form an elongated narrow focus, usually referred to as a 'needle' beam. The multiphoton lithography technique allows the realisation of almost any optical element on a fibre tip, thus providing the most suitable interface for free-space applications of multimode fibre-delivered laser beams. In addition, we demonstrate the optical trapping of microscopic objects with a super-focused multimode laser diode beam thus rising new opportunities within the applications sector where lab-on-chip configurations can be exploited. Most importantly, the demonstrated super-focusing approach opens up new avenues for the 'direct-diode' applications in material processing and 3D printing, where both high power and tight focusing is required.

A Raman spectroscopy bio-sensor for tissue discrimination in surgical robotics.

We report the development of a fiber-based Raman sensor to be used in tumour margin identification during endoluminal robotic surgery. Although this is a generic platform, the sensor we describe was adapted for the ARAKNES (Array of Robots Augmenting the KiNematics of Endoluminal Surgery) robotic platform. On such a platform, the Raman sensor is intended to identify ambiguous tissue margins during robot-assisted surgeries. To maintain sterility of the probe during surgical intervention, a disposable sleeve was specially designed. A straightforward user-compatible interface was implemented where a supervised multivariate classification algorithm was used to classify different tissue types based on specific Raman fingerprints so that it could be used without prior knowledge of spectroscopic data analysis. The protocol avoids inter-patient variability in data and the sensor system is not restricted for use in the classification of a particular tissue type. Representative tissue classification assessments were performed using this system on excised tissue.

Fundamentally mode-locked, femtosecond waveguide oscillators with multi-gigahertz repetition frequencies up to 15 GHz.

We demonstrate passively mode-locked Yb(3+)-doped glass waveguide lasers in a quasi-monolithic configuration with a maximum pulse repetition frequency up to 15.2 GHz. A semiconductor saturable absorber mirror (SESAM) is used to achieve stable mode-locking around 1050 nm with pulse durations as short as 811 fs and an average power up to 27 mW. Different waveguide samples are also employed to deliver pulses with repetition rates of 4.9 GHz, 10.4 GHz and 12 GHz with an average power of 32 mW, 60 mW and 45 mW, respectively. The group velocity dispersion control in the cavity is provided by changing the gap between the SESAM and the waveguide end-face to facilitate a soliton mode-locking regime.

Broadly tunable femtosecond Tm:Lu2O3 ceramic laser operating around 2070 nm.

Femtosecond mode locking of a Tm-doped Lu2O3 ceramic laser is reported. Transform-limited pulses as short as 180 fs are generated at 2076 nm with an average output power of 400 mW and a pulse repetition frequency of 121.2 MHz. An output power up to 750 mW can be reached at the somewhat longer pulse duration of 382 fs. Femtosecond pulse generation is realized in the 2030-2100 nm spectral range. Passive mode locking was achieved using an ion-implanted InGaAsSb quantum-well-based SESAM.

Passive mode locking of an in-band-pumped Ho:YLiF4 laser at 2.06 µm.

We demonstrate the passive mode-locking operation of an in-band-pumped Ho:YLiF(4) laser at 2.06 µm using a semiconductor saturable absorber mirror based on InGaAsSb quantum wells. A transform-limited pulse train with minimum duration of 1.1 ps and average power of 0.58 W has been obtained at a repetition frequency of 122 MHz. A maximum output power of 1.7 W has been generated with a corresponding pulse duration of 1.9 ps.

Enhanced operation of femtosecond lasers and applications in cell transfection.

In this work we present a review and discussion on the enhancement of femtosecond (fs) lasers for use within biophotonics with a particular focus on their use in optical transfection techniques. We describe the broad range of source options now available for the generation of femtosecond pulses before briefly reviewing the application of fs laser in optical transfection studies. We show that major performance enhancements may be obtained by optimising the spatial and temporal performance of the laser source before considering possible future directions in this field. In relation to optical transfection we describe how such laser sources initiate a multiphoton process to permeate the cell membrane in a transient fashion. We look at aspects of this technique including the ability to combine transfection with optical trapping. For future implementation of such transfection we explore the role of new sources and "nondiffracting" light fields.

Passive optical separation within a 'nondiffracting' light beam.

A passive, optical cell sorter is created using the light pattern of a 'nondiffracting' beam-the Bessel beam. As a precursor to cell sorting studies, microspheres are used to test the resolution of the sorter on the basis of particle size and refractive index. Variations in size and, more noticeably, refractive index, lead to a marked difference in the migration time of spheres in the Bessel beam. Intrinsic differences (size, refractive index) between native (unlabeled) cell populations are utilized for cell sorting. The large difference in size between erythrocytes and lymphocytes results in their successful separation in this beam pattern. The intrinsic differences in size and refractive index of other cells in the study (HL60 human promyelocytic leukaemic cells, murine bone marrow, and murine stem/progenitor cells) are not large enough to induce passive optical separation. Silica microsphere tags are attached to cells of interest to modify their size and refractive index, resulting in the separation of labeled cells. Cells collected after separation are viable, as evidenced by trypan blue dye exclusion, their ability to clone in vitro, continued growth in culture, and lack of expression of Caspase 3, a marker of apoptosis.

Thermographic assessment of tumor growth in mouse xenografts.

In human breast tumors, a 1-2 degrees C increase in skin surface temperature is usually observed at the periphery; it has been proposed that this change is due to the hypervascularity and increased blood flow resulting from tumor-associated angiogenesis. Here we tested the hypothesis that thermal imaging might represent a useful adjunctive technique in monitoring the growth dynamics of human tumor xenografts. Xenografts were established in immunocomprised nude mice using MDA-MB-231 or MCF7 breast cancer cells. We exploited the inherent noncontact and noninvasive advantages of infrared thermography to detect skin surface temperature changes. Continuous thermographic investigation was performed to detect and monitor tumor growth in vivo and high resolution digital images were analyzed to measure the tumor temperature dynamics. In contrast to the skin temperature increases associated with human breast cancer, a consistent temperature decrease was found in the xenograft mice. In one case, a smaller secondary tumor, otherwise undetectable, was clearly evident by thermal imaging. The tumors were cooler than the surrounding tissue with a maximum temperature reduction of 1.5 degrees C for MDA-MB-231 tumor and 3 degrees C for MCF7 tumors observed on day 14. In addition, the temperature of the xenograft tumors decreased progressively as they grew throughout the observation period. It was demonstrated that thermographic imaging could detect temperature changes as small as 0.1 degrees C on the skin surface at an early stage of tumor development. The findings of the study indicate that thermographic imaging might have considerable potential in monitoring human tumor xenografts and their response to anticancer drugs.

Optical trapping and fluorescence excitation with violet diode lasers and extended cavity surface emitting lasers.

Violet diode lasers and vertical extended cavity surface emitting lasers are used within an optical trapping system. Two distinct but related studies are performed. Firstly, the optical trapping efficiency in terms of the Q parameter for micron and sub-micron sized particles is determined. Secondly, we use the violet diode laser to observe and fluoresce 4'-6- Diamidino-2-phenylindole (DAPI) stained chromosomes, green fluorescent protein (GFP) transfected neuroblastomas, and fluorescent polymer spheres within an optical tweezers using a 1064nm trap laser. This work paves the way for both reduced trap volumes and for biological tagging, chromosome selection, or observing protein dynamics.

Brownian particle in an optical potential of the washboard type.

Experimental observations of the fluctuation-driven net transport of silica microspheres are presented in a two-dimensional optical potential of circular symmetry created by a Bessel light beam. The optical field is tailored to break symmetry and create a static tilted periodic (washboard) potential. As the tilt of potential exceeds a threshold, a transition between locked and running modes is observed. The running mode manifests itself by the rapid accumulation of particles at the beam center.