Nanobubbles - Electronics Research...

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Nanobubbles

Dr. Ari Salmi

14.2.2014 1


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


Physics of bubbles

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• 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


Bubbles and sound

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• 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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• Phase inversion imaging

• Reflections from linear reflectors (tissue) cancel out

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• 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)


Nanobubbles

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• 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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• 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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• 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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nanobubbles

• Also applicable for studying cells en masse

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nanobubbles

• Works also in vivo

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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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• Expanding/exploding nanobubbles/particles kill

cancer cells

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Take-home

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Take-home: Nanobubbles

• Nanobubbles can be used for

• Contrast enhancement

• Molecular imaging

• Theranostics

• Nanoscale damage generation (simulated)

Nanobubbles - Electronics Research...

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