8/11/2019 Optical trapping and acoustic excitation of microbubbles in a micro uidic system

http://slidepdf.com/reader/full/optical-trapping-and-acoustic-excitation-of-microbubbles-in-a-micro-uidic 1/1

    ©    Q   u   e   e   n    ’   s    P   r    i   n   t   e   r   a   n    d    C   o   n   t   r   o    l    l   e   r   o    f

    H    M    S    O ,    2    0    1    4 .

    1    0    9    6    9    /    0    7    1    4

Optical trapping and acoustic excitation ofmicrobubbles in a microfluidic system

Chris Fury1,2, Philip H. Jones2, Eleanor Stride3, Gianluca Memoli1

1Acoustics Group, National Physical Laborator y, Hampton Road, Teddington, TW11 0LW, UK 2Dept. of Physics and Astronomy, Universit y College London, Gower Street London, WC1E 6 BT, UK 

3Institute of Biomedical Engineering, Old Road Campus Research Building, University of Oxford, Oxford OX3 7DQ, UK 

 Acknowledgements The authors acknowledge financial 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

London’s IMPACT scheme.

References[1] Hernot, S., Klibanov, A. L., “Microbubblesin ultrasound-triggereddrugand genedelivery,”AdvancedDrugDelivery Reviews, 60, 1153-1166(2008).[2] Blomley, M. J. K., Cooke, J. C., Unger, E. C., Monaghan, M. J., Cosgrove, D. O., “Microbubblecontrast agents: a newera in ultrasound,”BMJ, 322, 1222 (2001).[

[3] Jones, P. H. , Stride, E. , Saffari. N., “Trappingandmanipulation of microscopic bubbleswith a scanningopticaltweezer,”Appl. Phys. Letters, 89, 081113(2006).

[4] Gahagan, K.T. , Swartzlander, G.A., “Trappingof lowindexparticles in an opticalvortex,”J. Opt. Soc. Am. B15, 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 andfiltration of low indexparticles with holographic Laguerre-Gaussian

opticaltrap arrays,”OpticsExpress, 12, 593-600(2004).

[6] Garbin, V. , Cojoc, D. , Ferrari, E., Di Fabrizio, E., Overvelde, M. L. J., van der Meer, S. M., deJong, N., Lohse, D., Versluis, M., “Changesin microbubble dynamicsnear a boundaryrevealedby combinedoptical

micromanipulation andhigh-speedimaging,”ApplPhysLett, 90, 114103 (2007).

[7] Jones. P. H., “OpticalTweezers,”[Encyclopedia of OpticalEngineering], 172, PP 1-16, DOI 10.1081/E-EOE-120047157[8] FuryC. R., HarfieldC. J., JonesP. H., StrideE. P. J. & Memoli G., “Experimentalcharacterisation of holographic opticaltraps for microbubbles”, Proc SPIE9126NanophotonicsV, 91263L (2014)

[9] BruusH. “Acoustofluidics7: Theacoustic radiation forceon smallparticles”, LabChip, 12, 1014 (2012)

[10] FuryC., Gélat P., Memoli G., JonesP. H., HodnettM., “Design andCharacterisation of a Microtransducer for MicrobubbleExcitation, AnnualSymposium of theUltrasonic IndustryAssociation”, in press

(2014)

[11] BassindaleP. G., PhillipsD. B., BarnesA. C., andDrinkwater B. W., “Measurementsof theforce fieldswithin an acoustic standingwaveusing holographic opticaltweezers”, AppliedPhysicsLetters, 104,

163504(2014)

 

3. Experimental results

• The maximum displacement occurs for low value of L, where the beam

shape is almost Gaussian (figure 3a).

• There is an optimum ratio of Γ =d trap / d bubble = 0.80 ±0.05 at which the

transverse spring constant is maximum (figure 3b).

• Radial trap stiffness 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

(figure 4). Pressures were obtained by fitting isolated bubble tracks with a

classical acoustophoresis model [9].

Figure 3. Dependence of (a) vertical displacement and (b) radial trap stiffness 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 phasegrating 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 fluctuations:

<x2> can be related to the

spring constant κ via

equipartition of energy [7].

1. Optical trapping

ChallengesLow 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 confined 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 fluctuations 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 fixed position.

4. Acoustic excitationRequirements• The excitation frequency needs to be in

the range 1-10 MHz.

• Pressure amplitudes, suffi 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 fit into the 300 m channel.

Solution• NPL designed an exponential

micro-transducer, which was

assembled at Meggit [10] (figure 5).

• The impedance, tested in water and

air, showed two main peaks, at 1182

kHz and 1240 kHz (figure 6).

• The pressure profile, obtained through hydrophone scans in a large water

tank, showed a different behaviour for the two peaks (fi gure 7).

5. In-channel operationExperimental set-up• The micro-transducer was inserted

in the microchip, which was filled

with Expancel bubbles at low

concentrations.

• Sinusoidal signals reached the

micro-transducer after amplification

(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 (fi gure 9).

• For 1182 kHz, a single peak was observed in hydrophone scanning, so this

frequency was selected for operation in the microfluidic chip.

• The distribution of pressure in the channel, monitored from above the

chip using a laser vibrometer, showed that the field reached the region

where bubbles are trapped (figure 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 (figure 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 beam around the

bubble [3, 4].

Use a Laguerre-Gaussian (LG or ‘doughnut’)

beam [5, 6].

IntroductionGas bubbles on the order of 1-10 m in radius and stabilized by a coati ng

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 effective and

cost-effective 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 finer 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 profile with a

300 m tip. Characterisation of this transducer’s 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 future1. 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 microfluidic manifold in presence of acoustic excitation from the

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 different 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 microfluidic chip.

Figure 4. Measurement of the acoustical trapping force on a bubble (8.2 m diam.) near a node of the

field (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)