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Optical trapping and acoustic excitation of
microbubbles in a microfuidic system
Chris Fury
1,2
, Philip H. Jones
2
, Eleanor Stride
3
, Gianluca Memoli
1
1
Acoustics Group, National Physical Laboratory, Hampton Road, Teddington, TW11 0LW, UK
2
Dept. of Physics and Astronomy, University College London, Gower Street London, WC1E 6BT, UK
3
Institute of Biomedical Engineering, Old Road Campus Research Building, University of Oxford, Oxford OX3 7DQ, UK
Acknowledgements
The authors acknowledge nancial support from the NPL Strategic Research
Fund (project 114248). ES acknowledges additional support from EPSRC (grant
EP/I021795/1). CF acknowledges additional support from University College
Londons IMPACT scheme.
References
[1] Hernot, S., Klibanov, A. L., Microbubbles in ultrasound-triggered drug and gene delivery, Advanced Drug Delivery Reviews, 60, 1153-1166 (2008).
[2] Blomley, M. J. K., Cooke, J. C., Unger, E. C., Monaghan, M. J., Cosgrove, D. O., Microbubble contrast agents: a new era in ultrasound, BMJ, 322, 1222 (2001).[
[3] Jones, P. H. , Stride, E. , Saari. N., Trapping and manipulation of microscopic bubbles with a scanning optical tweezer, Appl. Phys. Letters, 89, 081113 (2006).
[4] Gahagan, K.T. , Swartzlander, G.A., Trapping of low index particles in an optical vortex, J. Opt. Soc. Am. B 15, 524 (1998).
[5] Prentice, P. A., MacDonald, M. P., Frank, T. G., Cuschieri, A., Spalding, G. C., Sibbett, W., Campbell, P. A., Dholakia, K.. Manipulation and ltration of low index particles with holographic Laguerre-Gaussian
optical trap arrays, Optics Express, 12, 593-600 (2004).
[6] Garbin, V. , Cojoc, D. , Ferrari, E., Di Fabrizio, E., Overvelde, M. L. J., van der Meer, S. M., de Jong, N., Lohse, D., Versluis, M., Changes in microbubble dynamics near a boundary revealed by combined optical
micromanipulation and high-speed imaging, Appl Phys Lett, 90, 114103 (2007).
[7] Jones. P. H., Optical Tweezers, [Encyclopedia of Optical Engineering], 172, PP 1-16, DOI 10.1081/E-EOE-120047157
[8] Fury C. R., Hareld C. J., Jones P. H., Stride E. P. J. & Memoli G., Experimental characterisation of holographic optical traps for microbubbles, Proc SPIE 9126 Nanophotonics V, 91263L (2014)
[9] Bruus H. Acoustouidics 7: The acoustic radiation force on small particles, Lab Chip, 12, 1014 (2012)
[10] Fury C., Glat P., Memoli G., Jones P. H., Hodnett M., Design and Characterisation of a Microtransducer for Microbubble Excitation, Annual Symposiumof the Ultrasonic Industry Association, in press
(2014)
[11] Bassindale P. G., Phillips D. B., Barnes A. C., and Drinkwater B. W., Measurements of the force elds within an acoustic standing wave using holographic optical tweezers, Applied Physics Letters, 104,
163504 (2014)

3. Experimental results
The maximum displacement occurs for low value of L, where the beam
shape is almost Gaussian (gure 3a).
There is an optimum ratio of =d
trap
/d
bubble
= 0.80 0.05 at which the
transverse spring constant is maximum (gure 3b).
Radial trap stiness increases with laser power in the range 20-62 mW.
Optimum conditions were used to measure acoustical trapping forces
(163 kHz) on Expancel bubbles in the channel as a function of pressure
(gure 4). Pressures were obtained by tting isolated bubble tracks with a
classical acoustophoresis model [9].
Figure 3. Dependence of (a) vertical displacement and (b) radial trap stiness on L for two bubble
diameters (7 repeats each). Laser power was constant at 62 mW[8].
2. Materials and methods
Figure 1. Ray path schematic of the optical set-up.
Figure 2a. Trapping geometry.
Figure 2b. Size distribution of expanded Expancel
461-WU20. Inset shows the 50 bubbles used in this study.
Trapping laser: single mode
5W Nd:YAG (Laser Quantum).
Spatial light modulator (SLM):
XY Series, 256x256 pixels
(Boulder Non-Linear).
XY control: a blazed phase
grating across the beam.
Z control: a quadratic (lensing)
function (defocus).
Objective lens: PLAN APO IR,
60x, 1.27NA, water immersion
(Nikon).
CCD (70-90fps): for sample
observation and video
recordings (Thorlabs).
Glass microchannel:
enables the bubbles to be
manipulated simultaneously
with optical and acoustical
forces (Dolomite).
Bubbles: Expancel 461-WU20
(Akzo Nobel).
Data processing: video-
microscopy and particle
tracking analysis (Matlab).
Bubble position uctuations:
<x
2
> can be related to the
spring constant via
equipartition of energy [7].
1. Optical trapping
Challenges
Low relative refractive index objects, such as microbubbles suspended in
water, are more challenging to optically trap than high-index particles, as they
are strongly repelled from the waist of a focused Gaussian laser beam by both
scattering and gradient forces [3]. Microbubble trapping therefore requires
alternative strategies.
Possible solutions
In this study, the optical potential of a microbubble conned in a Laguerre-
Gaussian (LG or doughnut) beam trap was characterized by determining the
transverse spring constant for this geometry in terms of control parameters.
Measurements: video-microscopy of the
Brownian uctuations in the
microbubble position.
Modelling: a ray optics model of optically
trapped microbubbles in the
LG beam trap.
Exploitation
The displacement of bubbles in the optical tweezers was used to measure
acoustic trapping forces (~163 kHz) in a xed position.
4. Acoustic excitation
Requirements
The excitation frequency needs to be in
the range 1-10 MHz.
Pressure amplitudes, su cient to trigger
volume oscillations, need to reach the
area where bubbles are trapped.
A piston-like behaviour is required, to
avoid rupturing the glass slide.
The tip needs to t into the 300 m channel.
Solution
NPL designed an exponential
micro-transducer, which was
assembled at Meggit [10] (gure 5).
The impedance, tested in water and
air, showed two main peaks, at 1182
kHz and 1240 kHz (gure 6).
The pressure prole, obtained through hydrophone scans in a large water
tank, showed a dierent behaviour for the two peaks (gure 7).
5. In-channel operation
Experimental set-up
The micro-transducer was inserted
in the microchip, which was lled
with Expancel bubbles at low
concentrations.
Sinusoidal signals reached the
micro-transducer after amplication
(E&I A300) and custom impedance
matching electronics.
For 1240 kHz, laser refractometry showed that the angle of emission of the
two lobes depends on the depth of immersion (gure 9).
For 1182 kHz, a single peak was observed in hydrophone scanning, so this
frequency was selected for operation in the microuidic chip.
The distribution of pressure in the channel, monitored from above the
chip using a laser vibrometer, showed that the eld reached the region
where bubbles are trapped (gure 10).
6. Results
We observed aggregation of the bubbles at a distance comparable
with the wavelength in water at the excitation frequency (within 10%),
signalling that a standing wave was present (gure 11).
Preliminary value of force acting on the bubbles due to the
micro-transducer excitation was obtained from bubble tracking, in
absence of volume oscillations.
Scan a focused Gaussian beamaround the
bubble [3, 4].
Use a Laguerre-Gaussian (LG or doughnut)
beam[5, 6].
Introduction
Gas bubbles on the order of 1-10 m in radius and stabilized by a coating
of biological surfactant [1] have found use as contrast agents for ultrasound
imaging and, more recently, have shown a clear potential as targeted drug
delivery vectors [2]. The characterisation of the acoustical properties of
these microbubbles is important in order to validate simulations and
improve their design, thereby leading to safer, more clinically eective and
cost-eective medical products. In order to perform this characterization
at the single bubble level, a system has been constructed based upon
simultaneous use of optical and acoustical trapping (NPL sono-optical
tweezers), with the former providing the reference force calibration
and a ner manipulation than the latter.
Optical trapping has been achieved through the holographic encoding
of a Laguerre Gaussian mode on to a laser beam, providing a high intensity
repulsive ring which then holds the microbubbles. Results show clear
trends in optical trapping strengths, whereby the strength was seen to increase
with laser power and have an optimum value of the trap to bubble radius ratio.
Acoustic probing of the microbubbles at megahertz frequencies is achieved
with a custom designed transducer, employing an exponential prole with a
300 m tip. Characterisation of this transducers emission was conducted by
hydrophone scanning and by visualising the horn output through acousto-optic
laser vibrometry in a glass channel. Resulting acoustic pressure in the channel
will be discussed.
In the future
1. Full characterisation of the acoustic trapping forces (163 kHz) will be
obtained scanning the optical tweezers along the channel, as in [11].
2. Forces on the bubble due to the exciting transducer (~1 MHz) will
also be measured, with and without acoustic trapping in place.
3. Lipid-coated bubbles, with renonances in the range 1-3 MHz
will be excited and their dynamics will be observed using
high-speed photography.
(a) (b)
Figure 5. Exponential micro-transducer
used in this study.
Figure 6. Electrical impedance response of the
micro-transducer in air.
Figure 7. Hydrophone characterisation of the micro-transducer emission: (a) 1182 kHz; (b) 1240 kHz.
Figure 11. Aggregation of bubbles in the microuidic manifold in presence of acoustic excitation fromthe
micro-transducer. Measured wavelength was 1.1 0.1 mm.
Figure 8: Experimental set-up.
(a) (b)
Figure 9. Micro-transducer emission as seen by laser refractometry at dierent depths of immersion in a
water tank. As the tip enters the water, the intereferential pattern gets more complicated.
5.7 mm 5.8 mm 6.6 mm 7.5 mm 8.8 mm 11.0 mm
Figure 10. Pressure propagated in
the main channel, as seen by laser
refractometry through the top
surface of the microuidic chip.
Figure 4. Measurement of the acoustical trapping force on a bubble (8.2 mdiam.) near a node of the
eld (2 repeats): (a) displacement in the trap as a function of applied voltage and (b) measured force
as a function of applied pressure.
(a) (b)