Optical properties of gold nanorods: towards contrast agents for Photoacoustic imaging

C. Ungureanu, R. Raja Gopal , T. G. van Leeuwen & S. Manohar

Institute for BioMedical Technology

Institute for Biomedical Technology (BMTI), Biophysical Engineering Group, University of Twente Enschede, The Netherlands

Goal
Determine optical properties for gold nanorods: * Simulations using Discrete Dipole approximation * Experiments using spectrophotometry and photoacoustic Ultimate ambition to use these particles in vivo as: * Contrast agents for cancer detection * Vectors for photothermal therapy of cancer

Gold nanoparticles
Special properties due to surface plasmon resonance effect
0.9

Gold nanospheres
- Optical extinction peak ~ 520 nm Limited range of tunability
Absorbance (a.u)

0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

521.5

Photoacoustic imaging
Non-invasive imaging technique based on photoacoustic effect. Analyzes the ultrasound wave generated by an optical absorbing structure folowing irradiation with a short pulse of light. Mechanisms of generation: 1. Absorption of light 2. Emission of heat 3. Temperature rise 4. Thermal expansion 5. Stress wave Advantages: - Non invasive. - High resolution. - Spectroscopy. - Cheap.
pulsed laser acoustic wave absorber signal traces

25 nm diameter gold sphere

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wavelength (nm)

Gold nanorods
1.4

Absorbance (a.u)

* Two extinction peaks - transverse plasmon peak (510-530 nm). - longitudinal plasmon peal -LP (red shifted and tunable * Tunability in the region 700 -1100 nm

1.2 1.0 0.8 0.6

Extinction spectrum Length = 45.1 nm Width = 15.8 A.R.= 2.85

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516.5
0.4 0.2 0.0 450

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wavelength (nm)

Ideal for skin, breast and small animal imaging

ultrasound detectors

Attractive for NIR optical imaging

Optical properties simulations

* Discrete Dipole Approximation (DDSCAT) * Itterative method for computation * Calculate electromagnetic radiation scattered from particles of arbitrary shape * Particle discretized in N polarizable points

Validation
Simulation using Mie Theory and DDSCAT - Gold nanosphere of 12.5 nm radius)
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Choice of input parameters

1.1 1.0

Normalized absorbance (a.u)

1. Dielectric function

25 nm diameter gold sphere

0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 500 510

- Local refractive index of 1.33

Re(m)

-10 -20 -30 -40 -50 400 4 500 600 700 800 900 1000 1100 1200

1 - Dielectric function bulk gold - Number of dipoles 40000

1.1 1.0

Extinction spectrum DDSCAT (diel.func: Ref.1) DDSCAT (diel.func: Ref.2)

520 530 540 550 560 570 580 590 600

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wavelength (nm)
DDSCAT (diel.func: Ref.1) DDSCAT (diel.func: Ref.2) gold nanorod AR=3.55 844 872

Normalized absorbance (a.u)

Im (m)

0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 500

Extinction spectrum DDSCAT Mie Theory

3 2 1 0 400

Extinction efficiency (a.u)

DDSCAT (diel.func: Ref.1) DDSCAT (diel.func: Ref.2)

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Input information: - Size / Shape of the particle - Dielectric function - Local refractive index - Polarization of light

Output information: - Extinction efficiency - Absorption efficiency - Scattering eficiency - Anisotropy

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wavelength (nm)
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wavelength (nm)

1. P.B. Johnson and R.W. Christy, Optical Constants of the Noble Metals, Phys. Rev. B, vol. 6, Issue 12, pp. 4370-4379, (1972) 2. D. W. Lynch, W. R. Hunter. In Handbook of Optical Constants of Solids; Palik, E. D., Ed.; Academic Press:New York, (1985)

Gold sphere 25 nm diameter

510 520 530 540 550 560 570 580 590 600

2. Shape
17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 650 675 700 725 750 775 800 825 850 875 900

wavelength (nm)

The results closely match each other and experiments

B. T. Draine and P. J. Flatau, 2004, User Guide to the Discrete Dipole Approximation Code DDSCAT 6.1, http://arxiv.org/abs/astro-ph/0409262v2. 1. P.B. Johnson and R.W. Christy, Optical Constants of the Noble Metals, Phys. Rev. B, vol. 6, Issue 12, pp. 4370-4379, (1972)

Photoacoustic experiments
Experimental setup
Optical fiber

Extinction efficiency (a.u)

wavelength (nm)

From HR-SEM pictures the shape is spherically capped cylinder.

Great care must be taken when chosing the input parameters

700 nm-900 nm

Irradiate the nanorod solution with different wavelengths and fixed fluence

= Photoacoustic pressure = Constant = Absorption coefficient = Local fluence Photoacoustic spectrum

1.1 1.0 0.9

P = k a F
Extinction spectrum
3.5 3.0 2.5

k
a

Simulations results
Using:
Normalized absorbance (a.u)
1.2

measured extinction spectra calculated extinction spectra

1.0

F
Extinction spectrum 734

Size: from HR- SEM Shape: Sperically capped cylinder Dielectric function: From Ref [1] Local refractive index: 1.33

Length = 52 nm Width = 17.1 nm A.R. = 3.04

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Normalized amplitude

0.8 0.7 0.6 0.5 0.4

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Absorbance (a.u)

p ( ) a ( ) F ???
0.04 0.03 0.02 0.01 0.00

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-1 Extinction coefficient: 0.29 mm

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wavelength (nm)

0.3 0.2 0.1

photoaocustic signal

Concentration of particles = 5x1010 NR/ml Molar extinction coefficient = 15.2x10 M-1cm-1

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Qext Qabs Qsca GOLD NANOROD Length = 52 nm Width = 17.1 nm A.R. = 3.04

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Efficiency (a.u)

7 6 5 4 3 2 1 0 700

Amplitude (V)

wavelength (nm)
1.1

wavelength (nm)

Absorption coefficient = 0.26 mm

109 M-1cm-1

-1

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0.35

Extinction spectrum

780

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Normalized amplitude

-0.03

0.30

Absorbance (a.u)

0.8 0.7 0.6 0.5 0.4 0.3 0.2

-0.04 2 3 4 5 6 7 8 9 10 11 12

0.25

= 7.66 x : 40 nm Gold Sphere 4 -1 -1 = 1.08 x 10 M cm at 788 nm Indocyanine green = 1.16 x 105 M-1cm-1 at 530 nm Rhodamine 6G = 1.49 x 105 M-1cm-1 at 617 nm Malachite green

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wavelength (nm)

Time (s)

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Results compare favorably with experiments At this size of the particles, the extinction of light is dominated by absoprtion
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Shape of the photoacoustic spectrum agrees with the extinction spectrum Qualitative validation of simulation model

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1. P.B. Johnson and R.W. Christy, Optical Constants of the Noble Metals, Phys. Rev. B, vol. 6, Issue 12, pp. 4370-4379, (1972)

Conclusions
DDSCAT can be used to simulate optical properties of gold nanorods Attention is required when input parameters are chosen

Future
Validate quantitatively the results from simulations. Perform photoacoustic imaging using gold nanorods as contrast agents Study the nonlinear effects like bubble formation around gold nanorods

The photoacoustic spectrum agrees with the extinction spectrum. Study the hyperthermia Induced by laser on gold nanorods + cells