nanobubbles - electronics research...
TRANSCRIPT
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Nanobubbles
Dr. Ari Salmi
14.2.2014 1
www.helsinki.fi/yliopisto
Revisit to acoustic AFM
14.2.2014
Matemaattis-luonnontieteellinen tiedekunta /
Henkilön nimi / Esityksen nimi 2
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nc-AFM of molecules
• It takes 20 seconds to measure a single point
5 Å
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Why are the ends pronounced?
• Several reasons:
• Bonding order of C(1)–C(2), C(10)–C(11), C(12)–C(13)
and C(21)–C(22) bonds higher (1.6) than the other
bonds (1.1-1.4) stronger Pauli repulsion
5 Å
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Physics of bubbles
14.2.2014
Matemaattis-luonnontieteellinen tiedekunta /
Henkilön nimi / Esityksen nimi 5
• Cavities are formed with liquids are subjected to very
low pressures
• Start from cavitation nuclei (miniscule impurities)
• Inertial vs noninertial cavitation
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Cavitation
Lentacker et al., Soft Matter 2009
• Occurs when a bubble in a medium collapses quickly
• Emits a burst of light during the collapse
• Exact physical reason not known
• Bremsstrahlung, corona discharges, proton tunneling
etc.
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Sonoluminescence
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Bubbles and sound
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Matemaattis-luonnontieteellinen tiedekunta /
Henkilön nimi / Esityksen nimi 8
• Large impedance/mechanical property difference
between the gas-filled bubbles and the surrounding
medium
• Large reflection coefficient (strong echoes)
• Large translational forces
• Bubbles may also act as resonators
• May burst with large US amplitudes
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How do bubbles interact with
sound?
• Postema et al., W. J. Gast. 2011
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How do bubbles interact with
sound?
• Microbubbles are used as contrast enchancing
agents
• Frinking et al., UMBS 2000
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Contrast enhancement
• Features more clearly visible in the US pictures
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Contrast enhancement
• Phase inversion imaging
• Reflections from linear reflectors (tissue) cancel out
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Contrast enhancement
• E.g. Vicenzini et al., JUM 2008
• Maps the flow of e.g. drugs into vasculature
• Contrast from the bubbles
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Perfusion mapping
• Gas bubbles functionalized
• They are retained only at desired surfaces
‒ imaging of e.g. diseased areas!
‒ E.g. Klibanov, J. Nuc. Card 2007
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Molecular imaging
• Functionalized microbubbles
• Drug carrying capacity – optional targeting
‒ Disruption of the bubbles by US releases drugs
‒ E.g. Ferrara et al., Annu. Rev. Biomed. Eng. 2007
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Controlled drug release
• Oscillatory motion or jetting from the bubbles causes
an increase in permeability
• E.g. Cells, blood-brain barrier etc.
• E.g. Van Wamel et al., Journal of Controlled Release
2006
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Enhance permeability
• Dijkmans et al., Eur. J. Ech. 2004
• Bubbles stick to the thrombi and start to break them
down
• Also for litothripsy (Yoshizawa et al., Med. Biol. Eng.
Comp. 2009)
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Enhance HIFU (thrombolysis and
litothripsy)
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Nanobubbles
14.2.2014
Matemaattis-luonnontieteellinen tiedekunta /
Henkilön nimi / Esityksen nimi 19
• Taleyarkhan et al., Science 2002, PRL 2006
• Fusion by sonoluminescence
• Idea: Neutrons/alpha particles generate ~10-100 nm
bubble nuclei
• These nuclei are then expanded and rapidly collapse by
20 kHz ultrasound
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Let’s start off with some
controversial science
• They reported ~5000-10000 neutrons per second
from the fusions caused by the sonoluminescence
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Let’s start off with some
controversial science
• However, in repeated experiments the results have
not been replicated, e.g. Camara et al., PRL 2007
• They reported <1 neutron per second from SL
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Let’s start off with some
controversial science
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Let’s start off with some
controversial science
• Although some papers claim that there is evidence
(you will bump into these when doing research)
• There is no valid evidence of fusion generated by
nanobubble nuclei
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Concluding remarks on bubble
fusion
• Xing et al., Nanotechnology 2010
• Generation of nanobubbles from a batch of
microbubbles
• Perfluoropropane core filled with PFC
• Separation of nanobubbles by centrifugation
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Nanobubbles enhance contrast
• Enhances Doppler imaging resolution in a rabbit in
vivo
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Nanobubbles enhance contrast
• Wang et al., Langmuir 2011
• Functionalized ~400 nm diameter nanobubbles
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Molecular imaging with
nanobubbles
• Resulted in detection of leukemia-related T-cells
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Molecular imaging with
nanobubbles
• Lukianova-Hleb et al., PNAS 21.1.2014
• Photoacoustic generation of vapor nanobubbles (50-
400 nm) around hemozoins
• Malaria parasites digest hemoglobin and form
intraparasize hemozoin from it
• 532-672 nm, 20 ps to 14 ns excitation pulses
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Malaria detection with
nanobubbles
• Probe beam 633 nm < 0.1 mW continous beam
• Human malaria infected cells detected and
destroyed by the photoacoustically generated
nanobubbles
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Malaria detection with
nanobubbles
• Also applicable for studying cells en masse
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Malaria detection with
nanobubbles
• Works also in vivo
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Malaria detection with
nanobubbles
Blood sample
Through skin
• Shekhar et al., PRL 1.11.2013
• 1-billion atom MD simulation
• 163 840 processor supercomputer
• 67 million computing hours
• What happens when a shockwave hits a
nanobubble?
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Nanobubble cavitation in silica
• Pitting in silicon when the nanobubble collapses
• Nanojetting
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Nanobubble cavitation in silica
• Suzuki et al., J. Cont. Rel. 2011 and Cavalli et al.,
Int. J. Nanomed. 2012
• DNA-loaded 280 nm chitosan nanobubbles
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Nanobubble-based gene delivery
• DNA transjection into COS7 cells
• 30 second insonation
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Nanobubble-based gene delivery
• Shao et al., Scientific Reports 2013
• Functionalized gold nanobubbles attach to a cancer
tumor
• Probed with photoacoustics, exploded with higher
powers
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Nanobubble cancer theranostics
• PA signals detect and localize cancer cells
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Nanobubble cancer theranostics
• Expanding/exploding nanobubbles/particles kill
cancer cells
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Nanobubble cancer theranostics
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Take-home
14.2.2014
Matemaattis-luonnontieteellinen tiedekunta /
Henkilön nimi / Esityksen nimi 40
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Take-home: Nanobubbles
• Nanobubbles can be used for
• Contrast enhancement
• Molecular imaging
• Theranostics
• Nanoscale damage generation (simulated)