Prostate cancer (PCa) is a heterogeneous disease with multifocal origin. In current clinical care, the Gleason scoring system is the well-established diagnosis by microscopic evaluation of the tissue from trans-rectal ultrasound (TRUS) guided biopsies. Nevertheless, the sensitivity and specificity in detecting PCa can range from 40 to 50% for conventional TRUS B-mode imaging. Tissue elasticity is associated with the disease progression and elastography technique has recently shown promise in aiding PCa diagnosis. However, many cancer foci in the prostate gland has very small size less than 1 mm and those detected by medical elastography were larger than 2 mm. Hereby, we introduce optical coherence elastography (OCE) to quantify the prostate stiffness with high resolution in the magnitude of 10 µm. Following our feasibility study of 10 patients reported previously, we recruited 60 more patients undergoing 12-core TRUS guided biopsies for suspected PCa with a total of 720 biopsies. The stiffness of cancer tissue was approximately 57.63% higher than that of benign ones. Using histology as reference standard and cut-off threshold of 600kPa, the data analysis showed sensitivity and specificity of 89.6% and 99.8% respectively. The method also demonstrated potential in characterising different grades of PCa based on the change of tissue morphology and quantitative mechanical properties. In conclusion, quantitative OCE can be a reliable technique to identify PCa lesion and differentiate indolent from aggressive cancer.
We demonstrate a single channel hydrodynamic stretching microfluidic device that relies
on high-speed imaging to allow repeated dynamic cell deformation measurements. Experiments on
prostate cancer cells suggest richer data than current approaches.
The success of optical tweezers in cellular biology<sup>1</sup> is in part due to the wide range of forces that can be applied, from femto- to hundreds of pico-Newtons; nevertheless extending the range of applicable forces to the nanoNewton regime opens access to a new set of phenomena that currently lie beyond optical manipulation. <p> </p>A successful approach to overcome the conventional limits on trapping forces involves the optimization of the trapped probes. Jannasch <i>et al.</i><sup>2</sup> demonstrated that an anti-reflective shell of nanoporous titanium dioxide (<i>aTiO<sub>2</sub></i>, <i>n<sub>shell</sub></i> = 1.75) on a core particle made out of titanium dioxide in the anatase phase (<i>cTiO<sub>2</sub></i>, <i>n<sub>core</sub> </i>= 2.3) results in trappable microspheres capable to reach forces above 1 nN. <p> </p>Here we present how the technique can be further improved by coating the high refractive index microspheres with an additional anti-reflective shell made out of silica (<i>SiO<sub>2</sub></i>). This external shell not only improves the trap stability for microspheres of different sizes, but also enables the use of functionalization techniques already established for commercial silica beads in biological experiments. <p> </p>We are also investigating the use of these new microspheres as probes to measure adhesion forces between intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) in effector T-Cells and will present preliminary results comparing standard and high-index beads.
Advances in diagnostic technologies enabled scientists to link a large number of diseases with structural changes of the intracellular organisation. This intrinsic biophysical characteristic opened up the possibility to perform clinical assessments based on the measurement of single-cell mechanical properties. In this work, we combine microfluidics, high speed imaging and computational automatic tracking to measure the single-cell deformability of large samples of prostate cancer cells at a rate of ~ 10<sup>4</sup><i>cells/s</i>. Such a high throughput accounts for the inherent heterogeneity of biological samples and enabled us to extract statistically meaningful signatures from each cell population. In addition, using our technique we investigate the effect of <i>Latrunculin A</i> to the cellular stiffness.
The significant increase in the air pollution, and the impact on climate change due to the burning of fossil fuel has led to the research of alternative energies. Bio-ethanol obtained from a variety of feedstocks can provide a feasible solution. Mixing bio-ethanol with gasoline leads to a reduction in CO emission and in NOx emissions compared with the use of gasoline alone. However, adding ethanol leads to a change in the fuel evaporation. Here we present a preliminary investigation of evaporation times of single ethanol-gasoline droplets. In particular, we investigated the different evaporation rate of the droplets depending on the variation in the percentage of ethanol inside them. Two different techniques have been used to trap the droplets. One makes use of a 532nm optical tweezers set up, the other of an electrodynamics balance (EDB). The droplets decreasing size was measured using video analysis and elastic light scattering respectively. In the first case measurements were conducted at 293.15 K and ambient humidity. In the second case at 280.5 K and a controlled environment has been preserved by flowing nitrogen into the chamber. Binary phase droplets with a higher percentage of ethanol resulted in longer droplet lifetimes. Our work also highlights the advantages and disadvantages of each technique for such studies. In particular it is challenging to trap droplets with low ethanol content (such as pure gasoline) by the use of EDB. Conversely such droplets are trivial to trap using optical tweezers.
We introduce tunable optofluidic microlasers based on active optical resonant cavities formed by optically stretched, dye-doped emulsion droplets confined in a dual-beam optical trap. To achieve tunable dye lasing, optically pumped droplets of oil dispersed in water are stretched by light in the dual-beam trap. Subsequently, resonant path lengths of whispering gallery modes (WGMs) propagating in the droplet are modified, leading to shifts in the microlaser emission wavelengths. We also report lasing in airborne, Rhodamine B-doped glycerolwater droplets which were localized using optical tweezers. While being trapped near the focal point of an infrared laser, the droplets were pumped with a Q-switched green laser. Furthermore, biological lasing in droplets supported by a superhydrophobic surface is demonstrated using a solution of Venus variant of the yellow fluorescent protein or <i>E. Coli</i> bacterial cells expressing stably the Venus protein. Our results may lead to new ways of probing airborne particles, exploiting the high sensitivity of stimulated emission to small perturbations in the droplet laser cavity and the gain medium.
We present dye lasing from optically manipulated glycerol-water aerosols with diameters ranging between 7.7 and
11.0 μm confined in optical tweezers. While being optically trapped near the focal point of an infrared laser, the
droplets stained with Rhodamine B were pumped with a Q-switched green laser and their fluorescence emission
spectra featuring whispering gallery modes (WGMs) were recorded with a spectrograph. Nonlinear dependence
of the intensity of the droplet WGMs on the pump laser fluence indicates dye lasing. The average wavelength
of the lasing WGMs could be tuned between 600 and 630 nm by adjusting the droplet size. These results may
lead to new ways of probing airborne particles, exploiting the high sensitivity of stimulated emission to small
perturbations in the droplet laser cavity and the gain medium.
The increased application of holographic optical manipulation techniques within the life sciences has sparked the
development of accessible interfaces for control of holographic optical tweezers. Of particular interest are those that
employ familiar, commercially available technologies. Here we present the use of a low cost games console interface, the
Microsoft Kinect for the control of holographic optical tweezers and a study into the effect of using such a system upon
the quality of trap generated.
We present an optimized optical tweezers system based upon the conical refraction of circularly polarized light in a
biaxial crystal. The described optical arrangement avoids distortions to the Lloyd plane rings that become apparent when
working with circularly polarized light in conventional optical tweezers. We demonstrate that the intensity distribution of
the conically diffracted light permits optical manipulation of high and low refractive index particles simultaneously.
Such trapping is in three dimensions and not limited to the Lloyd plane rings. By removal of a quarter waveplate the
system also permits the study of linearly polarized conical refraction. We show that particle position in the Raman plane
is determined by beam power, and indicates that true optical tweezing is not taking place in this part of the beam.
We present a novel method for spatial mapping of the luminescent properties of single optically trapped semiconductor
nanowires by combing dynamic optical tweezers with micro-photoluminescence. The technique involves the use of a
spatial light modulator (SLM) to control the axial position of the trapping focus relative to the excitation source and
collection optics. When a nanowire is held in this arrangement, scanning the axial position of the trapping beam enables
different sections of the nanowire axis to be probed. In this context we consider the axial resolution of the luminescence
mapping and optimization of the nanowire trapping by spherical aberration correction.
The use of optical tweezers for the analysis of aerosols is valuable for understanding the dynamics of atmospherically
relevant particles. However to be able to make accurate measurements that can be directly tied to real-world phenomena
it is important that we understand the influence of the optical trap on those processes. One process that is seemingly
straightforward to study with these techniques is binary droplet coalescence, either using dual beam traps, or by particle
collision with a single trapped droplet. This binary coalescence is also of interest in many other processes that make use
of dense aerosol sprays such as spray drying and the use of inhalers for drug delivery in conditions such as asthma or hay
fever. In this presentation we discuss the use of high speed (~5000 frames per second) video microscopy to track the
dynamics of particles as they approach and interact with a trapped aqueous droplet and develop this analysis further by
considering elastic light scattering from droplets as they undergo coalescence. We find that we are able to characterize
the re-equilibration time of droplets of the same phase after they interact and that the trajectories taken by airborne
particles influenced by an optical trap are often quite complex. We also examine the role of parameters such as the salt
concentration of the aqueous solutions used and the influence of laser wavelength.
We investigated the occurrence of small but significant inaccuracies in the temporal integrity of a commercial high-speed
[rotating mirror] imaging system (a Cordin 550-62 camera). Utilizing a relatively straightforward hardware addition,
independent measurements of the actual frame rate at the point of camera triggering were conducted, and then compared
to the Cordin system's self-reported frame rate values for each recording. The present data thus represents a follow-up to
our earlier preliminary report on this instrument's performance, where we initially discovered that disparities between
the true and reported values could arise. Interestingly, the data trends observed in the present report suggest a disparity,
the nature of which is consistent with the Cordin camera reporting a frame rate that arises a short time <i>before</i> the trigger
event, i.e. that the system's sampling algorithm senses the frame rate with a finite pre-trigger implemented, which runs
counter to the procedure suggested by the manufacturer. As well as presenting the context, and supporting evidence for
our own conclusions, we also developed an approach to reduce the error in the reported values by a factor of 7, from an
average of 0.78% +/- 0.04% to 0.11% +/- 0.08% over the present data set.
High density micron sized aerosols from liquid surfaces were generated using surface acoustic wave (SAW)
nebulisation. The SAWs are made from a set of interdigitated electrodes (IDT) deposited on a lithium niobate (LiNbO<sub>3</sub>)
substrate and are designed to operate around 10MHz. RF powers of ~235mW are used to achieve nebulisation. Power
below this results in droplet motion across the substrate surface. The nebulisation process generated aerosols of a narrow
size distribution with diameter ranging from 0.5-2 μm. We consider ways in which these aerosols can be loaded into
optical traps for further study. In particular we look at how SAW nebulisation can be used to load particles into a trap in
a far more robust manner than a conventional nebuliser device. We demonstrate trapping of a range of particle types and
sizes and analyse the size distribution of particles as a function of the applied frequency to the SAW device. We show
that it is simpler to load, in particular, solid particles into optical traps using this technique compared to conventional
nebulisation. We also consider the possibilities for loading nanoparticles into aerosol optical tweezers.
When using single microfluidic droplets as isolated biological/chemical micro-reactors or arrays of droplets as 2D
assaying tools, control over droplet placement is crucial to successful device implementation. Here we demonstrate a
combined mechanical and optical approach to generate highly controllable arrays of droplets in pre-determined 'rails and
anchors' patterns on a two-dimensional plane.
The technique combines passive mechanical forcing with selective laser action. Passive mechanical forcing provides a
vehicle for droplet transport and storage and laser induced optical forcing is employed for stopping, guiding or derailing
droplets as they pass through the chip. In this way intelligent operations can be performed upon arrays of droplets such
as sorting, merging to initiate chemical reactions or selective removal of droplets from a predefined array. The usergenerated
array may then be held static against a mean flow for prolonged observation.
We demonstrate that light can be used to create microchannels in ice. We make use of free space and fiber coupled
infrared laser light to produce microchannels with diameters down to 100 microns in diameter. We demonstrate that the
channels can be created in a timescale of seconds and that by controlling the input power that they can be stabilized over
a timescale of several minutes using powers as low as 30mW. We compare the fiber coupled geometry, using both single
mode and multimode fiber and free space coupling and show that fiber coupling produces optimal results. We
demonstrate that liquid samples can be inserted into the channels and particle movement is observed using a combination
of optical and thermally induced forces. We also present data looking at droplet freezing within the microchannels. We
present preliminary results looking at dual beam coupling into such optofluidic channels and examine prospects for using
such channels as rapid microfluidic prototypes. We further discuss the possibility of using optically shaped ice channels
as a means to study aerosol nucleation processes and the ability of ice to act as a template for microfluidic devices.
We make use of a spatial light modulator to implement a phase-shifting interferometric method to determine the
topological charge of multiple singularities embedded in the transverse phase of singular beams. This method
allows us to discern between closely spaced singular points and elucidate the dynamics of optical vortices as their
charge is increased continually. The transverse phase of beams with a determined phase profile are analyzed
used this technique, yielding the precise location of multiple singularities as well as the value of their topological
charge. We use apply this method to accurately map the phase and study the transit of vortices across fractional
Bessel beams during their continuous order upconversion.
We present results describing the behavior of optically trapped airborne particles, both solid and liquid. Using back focal
plane interferometry we measure characteristic power spectra describing the position fluctuations within the trap. We
show it is easy to transfer between an over and under damped regime by either varying the trapping power or the
distance into the medium the beam is focused. The results assist in the understanding of airborne tweezers and it is hoped
having under damped systems could lead to exploring analogies in many areas of fundamental physics.
Aerosol tweezing with a super-continuum laser source has been successfully demonstrated. Salt-water droplets
in the range between 3 and 7 microns in diameters are trapped with a 300nm-wide super-continuum spectrum.
As the spectrum covers a few Mie resonances, the optical force is averaged and the trapping efficiency varies
smoothly with the square of the radius as in the case of the ray optics approximation. On-axis elastically back-scattered
spectrum allows a direct and precise determination of the trapped droplet. Evaporation of a single
droplet is precisely followed using this method. Alternative spectroscopic droplet sizing techniques are proposed
Droplet microfluidics is an emerging area in miniaturisation of chemical and biological assays, or "lab-on-a-chip"
devices. Normally consisting of droplets flowing in rigid microfluidic channels they offer many advantages over
conventional microfluidic design but lack any form of active control over the droplets. We present work, using
holographic beam shaping, that allows the real time reconfigurability of microfluidic channels allowing us to redirect,
slow, stop, and merge droplets with diameters of approximately 200 microns. A single beam is be sufficient to perform
simple tasks on the droplets but by using holographic beam shaping we can produce multiple foci or continuous patterns
of light that enable a far more versatile tool.
We discuss the application of optical trapping techniques to droplets, both in air (aerosols) and in fluid (emulsions). We show the holographic optical manipulation of aerosols and how this can be used to transfer orbital angular momentum to airborne particles. We demonstrate new types of traps for aerosols in the form of dual beam fibre traps and compare the trapping efficiency of IR and visible lasers. We discuss some of the interesting dynamics that can be observed when trapping airborne particles and how this appears to differ from conventional liquid based devices. We also examine how holographic optical trapping can be used to facilitate droplet manipulation in another liquid phase. We conclude with a discussion of the difficulties associated with trapping particles in air and possible solutions and well as look at some of the anticipated applications of such work, in particular in digital microfluidics.
The Brownian dynamics of an optically trapped water droplet is investigated across the transition from over to
under-damped oscillations. The spectrum of position fluctuations evolves from a Lorentzian shape typical of overdamped
systems (beads in liquid solvents), to a damped harmonic oscillator spectrum showing a resonance peak.
In this later under-damped regime, we excite parametric resonance by periodically modulating the trapping
power at twice the resonant frequency. We also derive from Langevin dynamics an explicit numerical recipe
for the fast computation of the power spectra of a Brownian parametric oscillator. The obtained numerical
predictions are in excellent agreement with the experimental data.
We demonstrate phase conjugation by means of degenerate four-wave mixing from a colloidal crystal. The nonlinear medium is provided by a periodic spatial refractive index grating created in a colloidal suspension of dielectric microparticles trapped in the intensity distribution of two nearly copropagating interfering laser beams. Phase conjugation is achieved for a probe beam carrying orbital angular momentum as evidenced by the inversion of the topological charge of a phase singularity within the beam. The e ciency and nonlinear parameters of the colloidal crystal as well as its lattice properties are measured and compared to theoretical predictions and previous experimental work.
Aerosol droplets are guided over mm distances using single beam optical traps. The micron-sized particles are confined in two dimensions and guided along the direction of beam propagation. Both Gaussian and Bessel beam geometries are compared for water, ethanol and dodecane droplets. The observed trapping of multiple droplets in 1-D arrays will also be discussed.
We demonstrate the use of holographic optical tweezers for the optical trapping and manipulation of arrays of airborne water droplets (aerosols). Making use of a phase-only spatial light modulator we present evidence of stable, interactive manipulation of both single and multiple aerosol droplets, of the order of 10 microns in diameter, and also their controlled coagulation. We discuss the advantages, disadvantages, and limitations of using a spatial light modulator for droplet manipulation including the implications of the update speed of the device (a Holoeye LC-R2500 SLM), diffraction efficiency, and droplet growth and evaporation due to laser intensity variations. We will examine the generic difficulties of trapping in air, working in the absence of inertial damping. Finally we will discuss the applications of the above work in fields such as atmospheric chemistry and microfluidic microchemical reactors whilst presenting preliminary results on fusion of two or more droplets of differing phases.
In the optical domain, the gradient force may be exploited in optical tweezers to confine high-index particles to points of maximum light intensity . This methodology has enabled key advances in biology enabling a deeper understanding of molecular motors and the properties of DNA. Optical traps have also enabled a wide range of studies in optical angular momentum, colloid science and microfluidics. Recent work has shown that extended, optically tailored landscapes can offer a mechanism by which to arrange and accumulate microparticles in pre-described arrays ). The ability to sculpt and reconfigure the optical potential energy landscape external to the sample is a key component of such studies. We
may add a tilt to the potential or, more generally, break symmetry, enabling unprecedented control over directed transport of particles  Three dimensional optical lattices may be used for sorting and fractionation of biological material in a microfluidic flow . However it would be advantageous to be able to separate and even accumulate both biological and colloidal matter in the absence of any flow within any sample chamber. This would allow true compatibility of sorting and separation without the need to implement flows and microfluidic systems. We exploit the varying affinity of mesoscopic objects to a circularly symmetric optical landscape to demonstrate this effect and demonstrate separation of cells and chromosomes. The differing Kramers residence time in each part of the light pattern
leads to a thermally activated method for sorting based on their hopping probabilities within the rings of the Bessel beam. Whilst we employ a Bessel beam to elucidate and demonstrate the dynamics of the sorting other tailored landscapes can also be used.
Optical micro-manipulation has seen a resurgence of interest in recent years which has been due in part to new application areas and the use of tailored forms of light beam. In this paper, experimental observations of fluctuation-driven transport of silica microspheres within a two-dimensional optical potential of circular symmetry are observed. The potential is created by a Bessel light beam. The optical field is tailored to break the symmetry and create a static tilted periodic (washboard) potential. Transitions between locked and running modes may be observed. The running mode manifests itself by rapid accumulation of particles at the beam centre. We discuss what happens with mixtures of particles in such an optical potential.
We demonstrate that counter-propagating light fields have the ability to create self-organized one-dimensional optically bound arrays of microscopic particles, where the light fields adapt to the particle locations and vice versa. We are able to create chains of up to 9 particles with only modest laser power. We outline the experimental observation of this phenomenon examining the effect of laser wavelength (780nm and 1064nm) and particle size (1, 2.3 and 3 micron diameter sphere sizes) on the interparticle separation. We develop a theoretical model to describe this situation making use of the beam propagation method to calculate the fields. Using the fields we are able to calculate the gradient and scattering forces experienced by the particles. Equilibrium positions in these forces indicate the predicted positions of the spheres. We find good agreement between the theory and experimental data for two and three particles, if the scattering force is assumed to dominate the axial trapping of the particles. We discuss the limitation of the model when dealing with spheres size of the order of the wavelength of light involved and also the experimental uncertainties relating to the measurement of the laser beam waist separations. The extension of these ideas to two and three dimensional optically bound states is also discussed.
Bessel beams have a number of properties that make them useful for optical manipulation. These include a central core which does not diffract over a characteristic distance, the reconstruction of the cross sectional intensity around obstacles and the ability of the beams to possess orbital angular momentum. Here we examine the utility of the Bessel beam to quantitatively examine the transfer of spin and orbital angular momentum to particle trapped away from the beam axis. We show the simultaneous transfer of orbital and spin angular momentum to an off-axis particle. We experimentally study how both the spin and orbital angular momentum of light behaves upon passage through microscopic optically trapped particles. Particles trapped with Gaussian and, separately, Bessel light beams in two spatially distinct sample chambers are studied with trapped objects in the first chamber acting as distorting obstacles. We examine the differences between Bessel beams and Gaussian beams in such experiments. We also show how the Bessel beam can be used to simultaneously trap particles that can be as much as 1cm away from each other. We discuss applications of these results and suggest other topics where the Bessel beam may be of use.
Optical micro-manipulation has seen a resurgence of interest in recent years, which has been due in part to new application areas and the use of tailored forms of light beam. In this paper, experimental observations of fluctuation-driven transport of silica microspheres within a two-dimensional optical potential of circular symmetry are observed. The potential is created by a Bessel light beam. The optical field is tailored to break the symmetry and create a static tilted periodic (washboard) potential. Transitions between locked and running modes may be observed. The running mode manifests itself by rapid accumulation of particles at the beam centre. We discuss what happens with mixtures of particles in such an optical potential.