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Title: Optical tweezers for the study of microbubble dynamics in ultrasound
Authors: Garbin, Valeria
Keywords: optical tweezersmedical imagingmolecular imaging applicationsbubble dynamics
Issue Date: 9-Mar-2007
Publisher: Università degli studi di Trieste
Abstract: Optical tweezers enable for non-destructive, contact-free manipulation of ultrasound contrast agent (UCA) microbubbles, which are used in medical imaging for enhancing the echogenicity of the blood pool and to quantify organ perfusion. Understanding the dynamics of ultrasound-driven contrast agent microbubbles from a fundamental physical standpoint is a first step for exploiting their acoustical properties and to develop new diagnostic and therapeutic applications. However, experiments on bubble dynamics presently suffer from a lack of control on bubble position, because of buoyancy, microstreaming and bubble clustering. In this respect, optical tweezers can be used to study UCA microbubbles under controlled and repeatable conditions, by positioning them away from interfaces and from neighboring bubbles. In addition, an ultra-high speed imaging system is required to record the dynamics of UCA microbubbles in ultrasound, as their oscillations occur on the nanoseconds timescale. In this thesis, optical tweezers and an ultra-high speed camera are integrated into an experimental setup to control the boundary conditions and record the oscillations of the microbubbles. Optical tweezers are commonly obtained by focusing a laser beam through a microscope objective, as the high intensity gradient in the focal region causes dielectric microparticles to be attracted in the focus. In the special case of microbubbles, which exhibit a lower refractive index than the surrounding liquid, the opposite situation arises: they are pushed away from the region of maximum intensity. Nevertheless, microbubbles can be trapped in the dark core of a donut-shaped trap, which can be obtained e.g. by focusing a Laguerre-Gaussian beam. In our setup, a Gaussian beam is converted to a Laguerre-Gaussian mode by using diffractive optical elements implemented on a spatial light modulator. This allows to trap and manipulate single or multiple microbubbles, and to control the distance from interfaces as well as the bubbleto- bubble distance. The “Brandaris 128” ultra-high speed camera is used, in combination with the optical tweezers, to recorded the bubble oscillations at a frame rate of 15 million frames per second. The influence of a rigid wall on the resonance frequency and oscillation amplitude was experimentally investigated. An experimental phospholipid-coated agent (BR-14, Bracco Research S.A., Geneva, Switzerland) was used throughout the experiments. A resonance frequency curve was recorded for the same bubble positioned at the wall and at controlled distance from the wall. The experiments show a drop in the resonance frequency for the bubble close to the ii Abstract wall, as expected from the theoretical models. These results are highly relevant for molecular imaging applications, where the response of targeted microbubbles needs to be discriminated from that of freely flowing ones. We also quantify the bubble-to-bubble interaction, in two ways: first, we compare the change of the radial oscillations of one bubble with and without a neighboring bubble. Second, we resolve the change in distance between two bubbles during ultrasonic insonation. This results from an acoustical, generally attractive, interaction force between the bubbles, termed secondary Bjerknes force. To understand this rich two-bubble dynamics, we couple a recent single-bubble model, accounting for both gas and monolayer properties with a model quantifying the mutual interaction of bubbles in their translation and oscillations. Experiments where optical tweezers are used as a force sensor to measure the binding force in an antigen-antibody complex at the single molecule level are also presented. In the future, the possibility of combining optical micromanipulation with the force-sensing capabilities of optical tweezers will open the way to a new class of experiments which will give us a deeper insight into fundamental bubble phenomena and find direct application to new ultrasound-assisted targeting strategies.
Description: 2005/2006
NBN: urn:nbn:it:units-3928
Appears in Collections:Scienze fisiche

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