Michael Mazilu

Optical manipulation of nanoparticles: a review

Optical trapping is an established field for movement of micron-size objects and cells. However, trapping of metal nanoparticles, nanowires, nanorods and molecules has received little attention. Nanoparticles are more challenging to optically trap and they offer ample new phenomena to explore, for example the plasmon resonance. Resonance and size effects have an impact upon trapping forces that causes nanoparticle trapping to differ from micromanipulation of larger micron-sized objects. There are numerous theoretical approaches to calculate optical forces exerted on trapped nanoparticles. Their combination and comparison gives the reader deeper understanding of the physical processes in an optical trap. A close look into the key experiments to date demonstrates the feasibility of trapping and provides a grasp of the enormous possibilities that remain to be explored. When constructing a single-beam optical trap, particular emphasis has to be placed on the choice of imaging for the trapping and confinement of nanoparticles.

Optical vortex trap for resonant confinement of metal nanoparticles.

The confinement and controlled movement of metal nanoparticles and nanorods is an emergent area within optical micromanipulation. In this letter we experimentally realise a novel trapping geometry near the plasmon resonance using an annular light field possessing a helical phasefront that confines the nanoparticle to the vortex core (dark) region. We interpret our data with a theoretical framework based upon the Maxwell stress tensor formulation to elucidate the total forces upon nanometric particles near the particle plasmon resonance. Rotation of the particle due to orbital angular momentum transfer is observed. This geometry may have several advantages for advanced manipulation of metal nanoparticles.

Early detection of cervical neoplasia by Raman spectroscopy

Early detection of malignant tumours, or their precursor lesions, improves patient outcome. High risk human papillomavirus (HPV), particularly HPV16, infection can lead to the development of uterine cervical neoplasia, and therefore, the identification in clinical samples of the effects of HPV infection may have clinical value. In this report, we apply Raman microspectroscopy to live and fixed cultured cells to discriminate between defined cell types. Raman spectra were acquired from primary human keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16‐containing cervical carcinoma‐derived cell line. Averaged Raman spectra showed variations, mostly in peaks originating from DNA and proteins, consistent with HPV gene expression and cellular changes associated with neoplasia, in both live and fixed cells. Principal component analysis produced good discrimination between the cell types, with sensitivities of up to 100% for the comparison of fixed PHK and CaSki. These results demonstrate the ability of Raman spectroscopy to discriminate between cell types representing different stages of cervical neoplasia. More specifically, this technique was able to identify cells expressing the HPV 16 E7 gene accurately and objectively, suggesting that this approach may be of value in diagnosis. Moreover, the ability to detect the effects of the virus in fixed samples also demonstrates the compatibility of Raman spectroscopy with current cervical screening methods.

Dual beam fibre trap for Raman micro-spectroscopy of single cells

Raman spectroscopy permits acquisition of molecular signatures from both cellular and sub-cellular samples. When combined with optical trapping we may interrogate an isolated cell reducing extraneous signals from the local environment. To date, experimental configurations have employed combinations of the single beam optical tweezers trap and Raman spectroscopy, using either the same beam or separate beams for Raman interrogation and trapping. A key problem in optical tweezers is the ability to hold and manoeuvre large cells. In this paper, we use a dual beam fibre trap to hold and manoeuvre cells combined with an orthogonally placed objective to record Raman spectra. The dual beam trap, due to its divergent light fields, offers an as yet unexploited ability to hold and move large cellular objects with reduced prospects of photodamage. We additionally show how this system permits us to move large primary human keratinocytes (approximately 30 microns in diameter), such that we may record Raman spectra from local parts of a trapped cell with ease. Finally, we develop a rudimentary microfluidic system used to generate a flow of cells. Using our dual beam trap, combined with this flow system, we hold and acquire Raman spectra from individual cells chosen from a sample of HL60 human promyelocytic leukemia cells.

Laser-induced rotation and cooling of a trapped microgyroscope in vacuum.

Quantum state preparation of mesoscopic objects is a powerful playground for the elucidation of many physical principles. The field of cavity optomechanics aims to create these states through laser cooling and by minimizing state decoherence. Here we demonstrate simultaneous optical trapping and rotation of a birefringent microparticle in vacuum using a circularly polarized trapping laser beam—a microgyroscope. We show stable rotation rates up to 5 MHz. Coupling between the rotational and translational degrees of freedom of the trapped microgyroscope leads to the observation of positional stabilization in effect cooling the particle to 40 K. We attribute this cooling to the interaction between the gyroscopic directional stabilization and the optical trapping field.

Dynamics of microparticles trapped in a perfect vortex beam

We trap and rotate particles using a perfect vortex beam with integer or fractional topological charges. A linear relationship is observed between the rotation speed and orbital angular momentum content of the beam.

In-fiber common-path optical coherence tomography using a conical-tip fiber

Common-path optical coherence tomography (CPOCT) is known to reduce group velocity dispersion and polarization mismatch between the reference and the sample arm as both arms share the same physical path. Existing implementations of CPOCT typically require one to incorporate an additional cover glass within the beam path of the sample arm to provide a reference signal. In this paper, we aim to further reduce this step by directly making use of the back-reflected signal, arising from a conical lens-tip fiber, as a reference signal. The conical lens, which is directly manufactured onto the optical fiber tip via a simple selective-chemical etching process, fulfils two functions acting as both the imaging lens and the self-aligning reference plane. We use a Fourier-domain OCT system to demonstrate the feasibility of this technique upon biological tissue. An in-fiber CPOCT technique may prove potentially useful in endoscopic OCT imaging.

Optical deflection and sorting of microparticles in a near-field optical geometry

Near-field optical micromanipulation permits new possibilities for controlled motion of trapped objects. In this work, we report an original geometry for optically deflecting and sorting micro-objects employing a total internal reflection microscope system. A small beam of laser light is delivered off-axis through a total internal reflection objective which creates an elongated evanescent illumination of light at a glass/water interface. Asymmetrical gradient and scattering forces from this light field are seen to deflect and sort polystyrene microparticles within a fluid flow. The speed of the deflected objects is dependent upon their intrinsic properties. We present a finite element method to calculate the optical forces for the evanescent waves. The numerical simulations are in good qualitative agreement with the experimental observations and elucidate features of the particle trajectory. In the size range of 1 microm to 5 microm in diameter, polystyrene spheres were found to be guided on average 2.9 +/- 0.7 faster than silica spheres. The velocity increased by 3.0 +/- 0.5 microms(-1) per microm increase in diameter for polystyrene spheres and 0.7 +/- 0.2 microms(-1) per microm for silica. We employ this size dependence for performing passive optical sorting within a microfluidic chip and is demonstrated in the accompanying video.

Online Fluorescence Suppression in Modulated Raman Spectroscopy

Label-free chemical characterization of single cells is an important aim for biomedical research. Standard Raman spectroscopy provides intrinsic biochemical markers for noninvasive analysis of biological samples but is often hindered by the presence of fluorescence background. In this paper, we present an innovative modulated Raman spectroscopy technique to filter out the Raman spectra from the fluorescence background. The method is based on the principle that the fluorescence background does not change whereas the Raman scattering is shifted by the periodical modulation of the laser wavelength. Exploiting this physical property and importantly the multichannel lock-in detection of the Raman signal, the modulation technique fulfills the requirements of an effective fluorescence subtraction method. Indeed, once the synchronization and calibration procedure is performed, minimal user intervention is required, making the method online and less time-consuming than the other fluorescent suppression methods. We analyze the modulated Raman signal and shifted excitation Raman difference spectroscopy (SERDS) signal of 2 mum-sized polystyrene beads suspended in a solution of fluorescent dye as a function of modulation rate. We show that the signal-to-noise ratio of the modulated Raman spectra at the highest modulation rate is 3 times higher than the SERDS one. To finally evaluate the real benefits of the modulated Raman spectroscopy, we apply our technique to Chinese hamster ovary cells (CHO). Specifically, by analyzing separate spectra from the membrane, cytoplasm, and nucleus of CHO cells, we demonstrate the ability of this method to obtain localized sensitive chemical information from cells, away from the interfering fluorescence background. In particular, statistical analysis of the Raman data and classification using PCA (principal component analysis) indicate that our method allows us to distinguish between different cell locations with higher sensitivity and specificity, avoiding potential misinterpretation of the data obtained using standard background procedures.

Planar photonic crystal polarization splitter

The differential dispersion relation for the E and H modes (TM-like and TE-like, respectively) in planar photonic crystals is used to control the polarization-dependent propagation of light. E- and H-polarized beams were separated by 10 degrees after propagating through a 20-microm-long planar photonic crystal in the wavelength range from 1250 to 1300 nm. The plane-wave expansion calculation matches well with the experimental results. This result represents the first demonstration, to our knowledge, of a polarization splitter realized in a planar photonic crystal configuration in the near-infrared wavelength range operating solely in transmission mode.