Optothermal manipulation of colloidal particles and biological objects

Optical based manipulation techniques play an important role in bottom-up assembly of micro- and nano-structures, discovery of new materials, and biomedical diagnostics. Traditional optical tweezers have limitations for the requirement of rigorous optics and high optical power. Optothermal manipulation, which exploits light-heat conversion and particle migration under a light-directed temperature field, is an emerging strategy for achieving diverse manipulation functionalities in a low-power fashion. In this work, we have developed a series of optothermal manipulation techniques, including bubble-pen lithography, opto-thermophoretic tweezers, opto-thermoelectric tweezers, and opto-thermoeletric printing. In bubble-pen lithography, microbubbles generated at solid-liquid interfaces through laser heating of a plasmonic substrate are used to pattern diverse colloidal particles on the substrate. Through directing the laser beam to move the bubble, we create arbitrary single-particle patterns and particle assemblies with different resolutions and architectures. The key to optothermal tweezers is the ability to achieve negative Soret effect, or deliver colloidal particles from cold to hot regions in a temperature field. Two types of optothermal tweezers with different driving forces are explored for versatile manipulation of colloidal particles and biological objects. Opto-thermophoretic tweezers rely on an abnormal permittivity gradient built by layered solvent molecules at the particle-solvent interface, while opto-thermoelectric tweezers exploit a thermophoresis-induced thermoelectric field for low-power trapping of nanoparticles. Furthermore, we have demonstrated opto-thermoelectric printing of colloidal particles on substrates in salt solutions and hydrogel solutions. With the low-power operation, simple optics, and diverse functionalities, optothermal manipulation techniques will find a myriad of applications in colloidal science, materials science, nanotechnology, and life sciences, as well as in developing functional colloidal devices and biomedical devices.Materials Science and Engineerin

Intracellular delivery by membrane disruption: Mechanisms, strategies, and concepts

© 2018 American Chemical Society. Intracellular delivery is a key step in biological research and has enabled decades of biomedical discoveries. It is also becoming increasingly important in industrial and medical applications ranging from biomanufacture to cell-based therapies. Here, we review techniques for membrane disruption-based intracellular delivery from 1911 until the present. These methods achieve rapid, direct, and universal delivery of almost any cargo molecule or material that can be dispersed in solution. We start by covering the motivations for intracellular delivery and the challenges associated with the different cargo typesñYsmall molecules, proteins/peptides, nucleic acids, synthetic nanomaterials, and large cargo. The review then presents a broad comparison of delivery strategies followed by an analysis of membrane disruption mechanisms and the biology of the cell response. We cover mechanical, electrical, thermal, optical, and chemical strategies of membrane disruption with a particular emphasis on their applications and challenges to implementation. Throughout, we highlight specific mechanisms of membrane disruption and suggest areas in need of further experimentation. We hope the concepts discussed in our review inspire scientists and engineers with further ideas to improve intracellular delivery

Characterisation of adherent microbubbles for molecular targeted ultrasound

Molecular imaging is a field of medicine which can offer great potential for both diagnostic and therapeutic purposes. Within this field contrast enhanced ultrasound displays the possibility of making molecular imaging a cost effective viable tool in an increasingly diverse set of clinical situations. One of the current challenges associated with this technique is how one differentiates the signal for adherent microbubbles from those produced by the bulk non-adherent population. The first part of this thesis acoustically examines the response of single microbubbles under the effects of adhesion and compares the response observed with that of the MBs non-adherent counterpart. It was found experimentally that differences could be observed in both the 2nd harmonic signals generation and in the stability over repeated exposure. These differences could be utilised as the basis for discretisation imaging strategies. The second section of this thesis attempts to characterize these differences in terms of current theoretical models. A more comprehensive modelling strategy is utilised for the fitting of increasingly complex theoretical models. Good agreement was found with the outputs of this fitting procedure with previously reported parameters. Further detail could also be observed in the form of various size/resonance effects which have not previously been reported. There was little observed difference between the parameters extracted for the adherent and non-adherent MBs although it was suggested that the effective elasticity of an adherent MB could be elevated in comparison to its non-adherent counterpart in the region of resonance. Efforts will be required to control and account for some of the variability observed in MB response before this can be stated definitively however.Open Acces

Sensitivity of photoacoustic microscopy

Building on its high spatial resolution, deep penetration depth and excellent image contrast, 3D photoacoustic microscopy (PAM) has grown tremendously since its first publication in 2005. Integrating optical excitation and acoustic detection, PAM has broken through both the optical diffusion and optical diffraction limits. PAM has 100% relative sensitivity to optical absorption (i.e., a given percentage change in the optical absorption coefficient yields the same percentage change in the photoacoustic amplitude), and its ultimate detection sensitivity is limited only by thermal noise. Focusing on the engineering aspects of PAM, this Review discusses the detection sensitivity of PAM, compares the detection efficiency of different PAM designs, and summarizes the imaging performance of various endogenous and exogenous contrast agents. It then describes representative PAM applications with high detection sensitivity, and outlines paths to further improvement

Whispering Gallery Modes: Advanced Photonic Applications

Los micro-resonadores basados en Whispering Gallery Modes (WGMs) han atraido un gran interés en las últimas décadas debido a su fuerte confinamiento de la luz. Tales micro-resonadores pueden ser fabricados con diferentes geometrías y materiales. Estos micro-resonadores exhiben factores de calidad Q altos y volúmenes modales pequeños, lo que permite realizar un gran número de estudios y aplicaciones, como por ejemplo el estudio de efectos no-lineales ópticos. La delgada anchura spectral que presentan las resonancias WGM permite la medida de pequeñas perturbaciones de los parámetros de los micro-resonadores, con un límite de detección bajo. Esta tesis proporciona la caracterización experimental de distintas propiedades de diferentes dispositivos fabricados en fibra óptica mediante los WGMs. El principio operacional de la técnicas de medida está basado en explotar la sintonización de las resonancias WGM mediante la variación de los parámetros que definen al material y la geometría de los micro-resonadores. Este método permite el estudio de las propiedades del micro-resonador midiendo la posición espectral de las resonancias WGM. La variación de los parámetros del micro-resonador puede estar inducida por deformaciones, por un cambio de temperatura, o por un campo magnético externo. La caracterización del efecto elasto-óptico en fibras ópticas de sílice y PMMA longitudinalmente estiradas permite la determinación de los coeficientes elasto-ópticos de ambos materiales. Comúnmente, un estiramiento axial genera una anisotropía uniaxial que puede ser medida directamente con nuestra técnica. Análogamente, la caracterización del efecto termo-óptico en diferentes dispositivos óptico en fibra, los cuales han sido iluminados con diferentes señales ópticas de potencia moderada, permite la medida de una variedad de parámetros: permite medir las contribuciones de la absorción y el scattering al coeficiente de atenuación en fibras fotosensibles irradiadas con luz Ultra-violeta, también permite medir los perfiles térmicos en redes de periodo largo (LPGs), y el calentamiento inducido ópticamente en fibras activas dopadas con diferentes elementos, como por ejemple el Holmio. Las principales características de la técnica experimental implementada son su bajo límite de detección, su resolución espacial, y su capacidad de medir los parámetros en un rango ancho de longitudes de onda, obteniendo así información de la dispersión cromática. Las técnicas de enganche son necesarias en experimentos que involucran WGMs, para así generar efectos no-lineales estables en el tiempo. Este trabajo propone dos nuevas técnicas de enganche para estabilizar el sistema mientras se trabaja a una longitud de onda operacional constante. Ambas técnicas están basadas en sintonizar la posición espectral de las resonancias WGM por medio de tensión axial, o una variación de la temperatura del micro-resonador. Finalmente, también se han estudiado efectos opto-mecánicos inducidos por la potencia del WGM el cual está circulando en la cavidad, lo que resulta en la excitación de modos acústicos en el micro-resonador. Los modos vibracionales con altos factores de calidad mecánicos fueron identificados y caracterizados en micro-resonadores con geometría de burbuja. Además, fue observado la transición hacia un comportamiento caótico del sistema a medida que la potencia del WGM fue incrementada.Whispering Gallery Modes (WGMs) based microresonators have attracted a great interest in the last decades due to their strong confinement of the light. Such microresonators can be fabricated with different geometries and materials. They exhibit high Q-factors and small mode volumes, which allows a great number of fundamental studies and applications, as for example the study of nonlinear phenomena. The narrow linewidths that the WGM resonances present enable the measurement of small perturbations of the microresonator parameters, with a low detection limit. This thesis provides an experimental characterization of the properties of different optical fiber devices by means of WGMs. The operational principle is based on exploiting the tunability of the WGM resonances by means of variations in the parameters that define the material and the geometry of the microresonators. This feature enables the study of the microresonator properties by measuring the optical spectral position of the WGM resonances. The variation of the microresonator’s parameters can be induced by strain, a temperature change, or an external magnetic field. The characterization of the strain-optic effect in silica and PMMA axially stretched optical fibers allowed the determination of the strain-optic coefficients of both materials. Commonly, an axial strain generates a uniaxial anisotropy that can be measured directly with our approach. Analogously, the characterization of the thermo-optic effect in different optical fiber devices, illuminated with different optical signals, enables the measurement of a variety of parameters: the contributions of absorption and scattering to the loss coefficient in UV-irradiated photosensitive fibers, thermal profiles in long period gratings, and the heating induced optically in active doped fibers. The main features of the implemented experimental technique are its low detection limit, its spatial resolution, and its capability to perform the measurements in a broad range of optical wavelengths. Locking techniques are necessary in experiments involving WGMs, to generate stable, nonlinear phenomena. This work provides two novel active locking techniques to stabilize the system at constant laser wavelength, which were experimentally tested. Both of them are based on the tuning of the spectral position of the WGM resonances either by means of axial strain, or temperature variations of the microresonators. Finally, optomechanical phenomena are a nonlinear effect induced by the high optical circulating power of the WGM, which results in the excitation of the acoustic modes of a microresonator. Vibrational resonant modes with high mechanical Q-factors were identified and characterized in bubble microresonators, and it was observed the transition to a chaotic behavior of this system, as the circulating power was increased

Nonlinear and Quantum Optics with Whispering Gallery Resonators

Optical Whispering Gallery Modes (WGMs) derive their name from a famous acoustic phenomenon of guiding a wave by a curved boundary observed nearly a century ago. This phenomenon has a rather general nature, equally applicable to sound and all other waves. It enables resonators of unique properties attractive both in science and engineering. Very high quality factors of optical WGM resonators persisting in a wide wavelength range spanning from radio frequencies to ultraviolet light, their small mode volume, and tunable in- and out- coupling make them exceptionally efficient for nonlinear optical applications. Nonlinear optics facilitates interaction of photons with each other and with other physical systems, and is of prime importance in quantum optics. In this paper we review numerous applications of WGM resonators in nonlinear and quantum optics. We outline the current areas of interest, summarize progress, highlight difficulties, and discuss possible future development trends in these areas.Comment: This is a review paper with 615 references, submitted to J. Op

Preparation of Tissues and Heterogeneous Cellular Samples for Single-Cell Analysis

While sample preparation techniques for the chemical and biochemical analysis of tissues are fairly well advanced, the preparation of complex, heterogenous samples for single-cell analysis can be difficult and challenging. Nevertheless, there is growing interest in preparing complex cellular samples, particularly tissues, for analysis via single-cell resolution techniques such as single-cell sequencing or flow cytometry. Recent microfluidic tissue dissociation approaches have helped to expedite the preparation of single cells from tissues through the use of optimized, controlled mechanical forces. Cell sorting and selective cellular recovery from heterogenous samples have also gained traction in biosensors, microfluidic systems, and other diagnostic devices. Together, these recent developments in tissue disaggregation and targeted cellular retrieval have contributed to the development of increasingly streamlined sample preparation workflows for single-cell analysis technologies, which minimize equipment requirements, enable lower processing times and costs, and pave the way for high-throughput, automated technologies. In this chapter, we survey recent developments and emerging trends in this field