Person: Yun, Seok-Hyun
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Yun
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Seok-Hyun
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Yun, Seok-Hyun
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Publication Wavelength-Encoded Laser Particles for Massively-Multiplexed Cell Tagging(Springer Nature, 2018-11-07) Martino, Nicola; Kwok, Sheldon; Forward, Sarah; Liapis, Andreas; Wu, Sarah; Dannenberg, Paul; Yun, Seok-Hyun; Jang, Hoon; Kim, Hwi-Min; Wu, Jiamin; Jang, Sun-Joo; Lee, Yong-HeeLarge-scale single-cell analyses have become increasingly important given the role of cellular heterogeneity in complex biological systems. However, no current techniques enable optical imaging of uniquely-tagged individual cells. Fluorescence-based approaches can only distinguish a small number of distinct cells or cell groups at a time because of spectral crosstalk between conventional fluorophores. Here we investigate large-scale cell tracking using intracellular laser particles as imaging probes that emit coherent laser light with a characteristic wavelength. Made of silica-coated semiconductor microcavities, these laser particles have single-mode emission over a broad range from 1170 to 1580 nm with sub-nm linewidths, enabling massive spectral multiplexing. We explore the stability and biocompatibility of these probes in vitro and their utility for wavelength-multiplexed cell tagging and imaging. We demonstrate real-time tracking of thousands of individual cells in a 3D tumour model over several days showing different behavioural phenotypes.Publication Wavelength-Encoded Laser Particles for Massively Multiplexed Cell Tagging(Springer Science and Business Media LLC, 2019-07-22) Martino, Nicola; Kwok, Sheldon; Liapis, Andreas; Forward, Sarah; Jang, Hoon; Kim, Hwi-Min; Wu, Sarah; Wu, Jiamin; Dannenberg, Paul; Jang, Sun-Joo; Lee, Yong-Hee; Yun, Seok-HyunLarge-scale single-cell analyses have become increasingly important given the role of cellular heterogeneity in complex biological systems. However, no current techniques enable optical imaging of uniquely-tagged individual cells. Fluorescence-based approaches can only distinguish a handful of distinct cells or cell groups at a time because of spectral crosstalk between conventional fluorophores. Here we show a novel class of imaging probes emitting coherent laser light, called laser particles. Made of silica-coated semiconductor microcavities, these laser particles have single-mode emission over a broad range from 1170 to 1580 nm with sub-nm linewidths, enabling massive spectral multiplexing. We demonstrate the stability and biocompatibility of these probes in vitro and their utility for wavelength-multiplexed cell tagging and imaging. We demonstrate real-time tracking of thousands of individual cells in a 3D tumor model for several days showing different behavioral phenotypes. We expect laser particles will enable new approaches for single-cell analyses.Publication Effects of Corneal Hydration on Brillouin Microscopy In Vivo(The Association for Research in Vision and Ophthalmology, 2018) Shao, Peng; Seiler, Theo G.; Eltony, Amira; Ramier, Antoine; Kwok, Sheldon; Scarcelli, Giuliano; Pineda, Roberto; Yun, Seok-HyunPurpose To investigate how corneal hydration affects the Brillouin frequency of corneal stroma. Methods: From a simple analytical model considering the volume fraction of water in corneal stroma, we derived the dependence of Brillouin frequency on hydration and hydration-induced corneal thickness variation. The Brillouin frequencies of fresh ex vivo porcine corneas were measured as their hydration was varied in dextran solution and water. Healthy volunteers (8 eyes) were scanned in vivo repeatedly over the course of 9 hours, and the diurnal variations of Brillouin frequency and central corneal thickness (CCT) were measured. Results: The measured dependence of Brillouin frequency on hydration, both ex vivo and in vivo, agreed well with the theoretical prediction. The Brillouin frequencies of human corneas scanned immediately after waking were on average ∼25 MHz lower than their daytime average values. For stabilized corneas, the typical variation of Brillouin frequency was ± 7.2 MHz. With respect to CCT increase or swelling, the Brillouin frequency decreased with a slope of −1.06 MHz/μm in vivo. Conclusions: The ex vivo and in vivo data agree with our theoretical model and support that the effect of corneal hydration on Brillouin frequency comes predominantly from the dependence of the tissue compressibility on the water. Corneal hydration correlates negatively with the Brillouin frequency. During daytime activities, the influence of physiological hydration changes in human corneas is < ± 10 MHz. The sensitivity to hydration may potentially be useful in detecting abnormal hydration change in patients with endothelial disorders.Publication On the near-wall accumulation of injectable particles in the microcirculation: smaller is not better(Nature Publishing Group, 2013) Lee, Tae-Rin; Choi, Myunghwan; Kopacz, Adrian M.; Yun, Seok-Hyun; Liu, Wing Kam; Decuzzi, PaoloAlthough most nanofabrication techniques can control nano/micro particle (NMP) size over a wide range, the majority of NMPs for biomedical applications exhibits a diameter of ~100 nm. Here, the vascular distribution of spherical particles, from 10 to 1,000 nm in diameter, is studied using intravital microscopy and computational modeling. Small NMPs (≤100 nm) are observed to move with Red Blood Cells (RBCs), presenting an uniform radial distribution and limited near-wall accumulation. Larger NMPs tend to preferentially accumulate next to the vessel walls, in a size-dependent manner (~70% for 1,000 nm NMPs). RBC-NMP geometrical interference only is responsible for this behavior. In a capillary flow, the effective radial dispersion coefficient of 1,000 nm particles is ~3-fold larger than Brownian diffusion. This suggests that sub-micron particles could deposit within diseased vascular districts more efficiently than conventional nanoparticles.Publication Numerical model of optical coherence tomographic vibrography imaging to estimate corneal biomechanical properties(The Royal Society, 2014) Kling, Sabine; Akca, Imran B.; Chang, Ernest W.; Scarcelli, Giuliano; Bekesi, Nandor; Yun, Seok-Hyun; Marcos, SusanaMost techniques measuring corneal biomechanics in vivo are biased by side factors. We demonstrate the ability of optical coherence tomographic (OCT) vibrography to determine corneal material parameters, while reducing current prevalent restrictions of other techniques (such as intraocular pressure (IOP) and thickness dependency). Modal analysis was performed in a finite-element (FE) model to study the oscillation response in isolated thin corneal flaps/eye globes and to analyse the dependency of the frequency response function on: corneal elasticity, viscoelasticity, geometry (thickness and curvature), IOP and density. The model was verified experimentally in flaps from three bovine corneas and in two enucleated porcine eyes using sound excitation (100–110 dB) together with a phase-sensitive OCT to measure the frequency response function (range 50–510 Hz). Simulations showed that corneal vibration in flaps is sensitive to both, geometrical and biomechanical parameters, whereas in whole globes it is primarily sensitive to corneal biomechanical parameters only. Calculations based on the natural frequency shift revealed that flaps of the posterior cornea were 0.8 times less stiff than flaps from the anterior cornea and cross-linked corneas were 1.6 times stiffer than virgin corneas. Sensitivity analysis showed that natural vibration frequencies of whole globes were nearly independent from corneal thickness and IOP within the physiological range. OCT vibrography is a promising non-invasive technique to measure corneal elasticity without biases from corneal thickness and IOP.Publication Reconfigurable optical assembly of nanostructures(Nature Publishing Group, 2016) Montelongo, Yunuen; Yetisen, Ali K.; Butt, Haider; Yun, Seok-HyunArrangements of nanostructures in well-defined patterns are the basis of photonic crystals, metamaterials and holograms. Furthermore, rewritable optical materials can be achieved by dynamically manipulating nanoassemblies. Here we demonstrate a mechanism to configure plasmonic nanoparticles (NPs) in polymer media using nanosecond laser pulses. The mechanism relies on optical forces produced by the interference of laser beams, which allow NPs to migrate to lower-energy configurations. The resulting NP arrangements are stable without any external energy source, but erasable and rewritable by additional recording pulses. We demonstrate reconfigurable optical elements including multilayer Bragg diffraction gratings, volumetric photonic crystals and lenses, as well as dynamic holograms of three-dimensional virtual objects. We aim to expand the applications of optical forces, which have been mostly restricted to optical tweezers. Holographic assemblies of nanoparticles will allow a new generation of programmable composites for tunable metamaterials, data storage devices, sensors and displays.Publication Flexible Optical Waveguides for Uniform Periscleral Cross-Linking(The Association for Research in Vision and Ophthalmology, 2017) Kwok, Sheldon; Kim, Moonseok; Lin, Harvey H.; Seiler, Theo G.; Beck, Eric; Shao, Peng; Kochevar, Irene; Seiler, Theo; Yun, Seok-HyunPurpose Scleral cross-linking (SXL) with a photosensitizer and light is a potential strategy to mechanically reinforce the sclera and prevent progressive axial elongation responsible for severe myopia. Current approaches for light delivery to the sclera are cumbersome, do not provide uniform illumination, and only treat a limited area of sclera. To overcome these challenges, we developed flexible optical waveguides optimized for efficient, homogeneous light delivery. Methods: Waveguides were fabricated from polydimethylsiloxane elastomer. Blue light (445 nm) is coupled into the waveguide with an input fiber. Light delivery efficiency from the waveguide to scleral tissue was measured and fit to a theoretical model. SXL was performed on fresh porcine eyes stained with 0.5% riboflavin, using irradiances of 0, 25, and 50 mW/cm2 around the entire equator of the eye. Stiffness of scleral strips was characterized with tensiometry. Results: Light delivery with a waveguide of tapered thickness (1.4–0.5 mm) enhanced the uniformity of light delivery, compared to a flat waveguide, achieving a coefficient of variation of less than 10%. At 8% strain, sclera cross-linked with the waveguides at 50 mW/cm2 for 30 minutes had a Young's modulus of 10.7 ± 1.0 MPa, compared to 5.9 ± 0.5 MPa for no irradiation, with no difference in stiffness between proximally and distally treated halves. The stiffness of waveguide-irradiated samples did not differ from direct irradiation at the same irradiance. Conclusions: We developed flexible waveguides for periscleral cross-linking. We demonstrated efficient and uniform stiffening of a 5-mm-wide equatorial band of scleral tissue.Publication Parametric Simulations of Slanted 1D Photonic Crystal Sensors(Springer US, 2016) Breuer-Weil, Aaron; Almasoud, Naif Nasser; Abbasi, Badaruddin; Yetisen, Ali K.; Yun, Seok-Hyun; Butt, HaiderPhotonic crystals and band gap materials act as manipulators of light and have a plethora of applications. They are made up of stacks of alternating dielectric constants. This article shows the simulations of an inclined, one dimensional and tuneble photonic crystal, using numerical finite element methods. The photonic crystal was made up of silver nanoparticles embedded in a hydrogel matrix and it has the ability to change and recover its periodicity. A series of factors concerning the geometry of the lattice were tested in order to analyze the efficiency, performance and optimize the properties of the optical sensor. These factors range from the size of the nanoparticles and their density within the stacks, to observing the effect of diffraction angle in readouts.Publication Two-photon excited photoconversion of cyanine-based dyes(Nature Publishing Group, 2016) Kwok, Sheldon; Choi, Myunghwan; Bhayana, Brijesh; Zhang, Xueli; Ran, Chongzhao; Yun, Seok-HyunThe advent of phototransformable fluorescent proteins has led to significant advances in optical imaging, including the unambiguous tracking of cells over large spatiotemporal scales. However, these proteins typically require activating light in the UV-blue spectrum, which limits their in vivo applicability due to poor light penetration and associated phototoxicity on cells and tissue. We report that cyanine-based, organic dyes can be efficiently photoconverted by nonlinear excitation at the near infrared (NIR) window. Photoconversion likely involves singlet-oxygen mediated photochemical cleavage, yielding blue-shifted fluorescent products. Using SYTO62, a biocompatible and cell-permeable dye, we demonstrate photoconversion in a variety of cell lines, including depth-resolved labeling of cells in 3D culture. Two-photon photoconversion of cyanine-based dyes offer several advantages over existing photoconvertible proteins, including use of minimally toxic NIR light, labeling without need for genetic intervention, rapid kinetics, remote subsurface targeting, and long persistence of photoconverted signal. These findings are expected to be useful for applications involving rapid labeling of cells deep in tissue.Publication Line-scanning Brillouin microscopy for rapid non-invasive mechanical imaging(Nature Publishing Group, 2016) Zhang, Jitao; Fiore, Antonio; Yun, Seok-Hyun; Kim, Hanyoup; Scarcelli, GiulianoBrillouin spectroscopy probes the mechanical properties of material by measuring the optical frequency shift induced by photon-phonon scattering interactions. In traditional configurations, Brillouin spectrometers measure only one point of the sample at a time. This results in long acquisition times for mechanical imaging of large areas. In this work, we demonstrate a parallel detection configuration where the Brillouin shift of hundreds of points in a line can be measured simultaneously. In mm-sized samples, this novel configuration effectively shortens the acquisition time of two-dimensional Brillouin imaging from hours to tens of seconds, thus making it a powerful technology for label-free mechanical characterization of tissue and biomaterials.