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Title: Optical tweezers for the study of microbubble dynamics in ultrasound
Authors: Garbin, Valeria
Supervisore/Tutore: Di Fabrizio, Enzo
Cosupervisore: Tommasini, Fernando
Cojoc, Danut Adrian
Versluis, Michel
Issue Date: 9-Mar-2007
Publisher: Università degli studi di Trieste
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
Ciclo di dottorato: XIX Ciclo
metadata.dc.subject.classification: NANOTECNOLOGIE
Keywords: optical tweezersmedical imagingmolecular imaging applicationsbubble dynamics
Type: Doctoral
Language: en
NBN: urn:nbn:it:units-3928
Appears in Collections:Scienze fisiche

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