Effects of physicochemical properties of particles and medium on acoustic pressure pulses from laser-irradiated suspensions

Colloids and Surfaces A: Physicochem. Eng. Aspects 487 (2015) 42–48

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Effects of physicochemical properties of particles and medium on acoustic pressure pulses from laser-irradiated suspensions Tomonori Fukasawa a,b , Shota Noguchi a , Hiroyuki Shinto c,∗ , Hiroyuki Aoki d,e , Shinzaburo Ito d , Masahiro Ohshima a a

Department of Chemical Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan Department of Chemical Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8527, Japan c Department of Chemical Engineering, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan d Department of Polymer Chemistry, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan e Advanced Biomedical Engineering Research Unit, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan b

h i g h l i g h t s

g r a p h i c a l

a b s t r a c t

• Photoacoustic (PA) phenomena of nanoparticle (NP) suspensions are studied. • PA pressures from aqueous suspensions of metal and polymer NPs are measured. • The effects of NP material, NP size, and temperature on PA pressure are investigated. • The experimental results are compared with the estimations from a physical model.

a r t i c l e

i n f o

Article history: Received 15 July 2015 Received in revised form 9 September 2015 Accepted 17 September 2015 Available online 21 September 2015 Keywords: Photoacoustic imaging Photoacoustic pressure Physicochemical properties Metal nanoparticles Polymer nanoparticles Contrast agents

a b s t r a c t We experimentally measured the photoacoustic responses from monodispersed suspensions of spherical nanoparticles (NPs) of metal (gold, diameter = 9.4, 19.9, 40.2, 49.3, and 59.9 nm) and dye-containing polymer (polystyrene, diameter = 63.1, 73.0, 85.9, and 93.7 nm) in water at different NP concentrations and temperatures (4, 20, and 37 ◦ C), where the samples were irradiated with 5-ns laser pulses at low laser fluence. The obtained experimental results were explained by a physical model, where the acoustic pressure pulse was represented by a sum of two contributions from the NPs and the surrounding liquid medium. These results revealed that the photoacoustic responses from a laser-irradiated NP suspension are influenced by the physicochemical properties of the NPs and medium. We also proposed a strategy on how to design NPs for photoacoustic contrast imaging on the basis of obtained results. © 2015 Elsevier B.V. All rights reserved.

1. Introduction Photoacoustic (PA) imaging is one of rapidly growing techniques for biomedical imaging, because it is a noninvasive imaging

∗ Corresponding author. Fax: +81 92 865 6031. E-mail address: [email protected] (H. Shinto). http://dx.doi.org/10.1016/j.colsurfa.2015.09.051 0927-7757/© 2015 Elsevier B.V. All rights reserved.

modality with the advantages of both optical and acoustic imaging techniques. The PA imaging technique utilizes a PA effect, which results from the conversion of absorbed light into acoustic waves that can be detected outside of the subject of interest. The contrast in PA imaging depends on the optical-to-acoustic conversion efficiency and can be improved greatly by using nanoparticles (NPs) as contrast agents [1–6]. Photoacoustic flow cytometry (PAFC) also relies on this NP-induced PA contrast enhancement to detect

T. Fukasawa et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 487 (2015) 42–48

various circulating targets (e.g., circulating tumor cells, circulating blood clots, and pathogens) in living systems [6–9]. Various NPs have been synthesized for the PA contrast agents, such as nanostructured metal particles [10–15], carbon nanotubes [16,17], and dye-containing NPs [18–20]. The focus of these studies has been placed on how to improve the optical absorption efficiency of the NPs, because the amplitude of PA signal increases with increasing absorption efficiency [21]. Recently, Chen et al. have shown that the PA signals generated from laser-irradiated suspensions of silica-coated gold nanorods [22,23] and nanospheres [24] are influenced by the thickness of silica shells. They also have demonstrated that the PA signals from the suspensions of spherical 26-nm gold NPs are influenced by the temperature-dependent properties of the host liquid media and are dominated by the contribution from the surrounding media rather than that from the gold NPs themselves [24]. These results have revealed that the PA signal generated from a particle suspension is affected not only by the optical absorption efficiency of the particles, but also by the physicochemical properties of the surrounding medium and the particle–medium interface. Our previous study has demonstrated that the amplitude of PA signal generated from the aqueous suspension of spherical gold NPs at an ambient temperature decreases with increasing particle size [25]. This dependence of the PA signal amplitude on the particle size is explained by our phenomenological model [25,26], where the PA pulse is represented by a sum of two contributions from the NPs and the medium. In contrast, Aoki et al. have reported that the PA signal amplitudes from the aqueous suspensions of polymer NPs containing dyes increase with particle size [27]. This difference in particle-size dependence of the PA signal amplitude between the aqueous suspensions of gold NPs and those of polymer NPs would be attributable to the difference in physicochemical properties between gold and polymers. Nevertheless, the effects of physicochemical properties of NPs on the PA phenomena are not well understood and remain to be explored experimentally and theoretically from a fundamental point of view. The present study reports the experimental and theoretical results on how the physicochemical properties of NPs and medium influence the PA responses from a laser-irradiated suspension. We have carried out the measurements of PA signals, where the suspensions of spherical gold and polystyrene (PS) NPs with different diameters in water at different temperatures are irradiated with nanosecond laser pulses at low laser fluence. The results from the experiments are compared with those obtained from a phenomenological model developed in our previous studies [25,26]. We also propose a strategy on how to design NPs for PA contrast imaging on the basis of our findings.

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Table 1 Suspensions of the gold NPs and the DiI-containing PS NPs for measurements of PA responses. Dispersoid

Diameter dp (nm)

Optical density at ex = 560 nm OD560 (−)

Temperature Tinit (◦ C)

Au-10 Au-20 Au-40 Au-50 Au-60 PS-63 PS-73 PS-86 PS-94

9.4 19.9 40.2 49.3 59.9 63.1 73.0 85.9 93.7

0.033, 0.093, 0.208 0.065, 0.122, 0.206 0.057, 0.124, 0.260 0.081, 0.178, 0.324 0.107, 0.238, 0.323 0.086, 0.193, 0.279 0.142, 0.185, 0.275 0.096, 0.151, 0.186 0.094, 0.176, 0.297

4, 20, 37 4, 20, 37 4, 20, 37 4, 20, 37 4, 20, 37 4, 20, 37 4, 20, 37 4, 20, 37 4, 20, 37

2.2. Dye-containing polymer nanoparticles NPs of a polymer containing dyes were prepared via a nanoemulsion method. The polymer, dye, and surfactant used in the present study were polystyrene (PS, approximate M.W. = 22000; Scientific Polymer Products, NY, USA), 1,1 dioctadecyl-3,3,3 3 -tetramethylindocarbocyanine perchlorate (DiI; PromoKine, Heidelberg, Germany), and sodium dodecyl sulfate (SDS; Tokyo Chemical Industry, Tokyo, Japan), respectively. Chloroform was purchased from Nacalai Tesque (Kyoto, Japan). These reagents were of analytical grades and used without further treatment. All water used in the experiments was purified using a Direct-Q 3 UV system (Merck Millipore, Darmstadt, Germany) to give a resistance of 18.2 M cm and a total organic carbon of less than 5 ppb. A typical preparation procedure for the dye-containing polymer NPs is described elsewhere [27]. Briefly, 800 ␮L of a chloroform solution containing PS (5 or 10 mg/mL) and DiI (0.25 or 0.50 mg/mL), where the DiI/PS ratio was fixed at 0.05, was added to 10 mL of an aqueous solution containing SDS (1, 2, or 4 mg/mL). The oil phase was emulsified via ultrasonication at a frequency of 22.5 kHz and a power of 20 W (Microson XL2000; Misonix, NY, USA) for 30 s at 0 ◦ C. The emulsified solution was stirred at 40 ◦ C for 90 min, whereby the chloroform was allowed to evaporate and removed from the solution. The DiI-containing PS NPs obtained were washed three times by a series of centrifuge filtration (Nanosep 100K Omega; PALL, NY, USA) at 5000 × g for 7 min (Model 3500; KUBOTA, Tokyo, Japan) and redispersion in water. As summarized in Table S1 of Supplementary data, a variation of the PS and SDS concentrations enabled us to obtain the PS NPs with different diameters (dp = 63.1, 73.0, 85.9, and 93.7 nm), which were estimated by dynamic light scattering with ELSZ-2 (Otsuka Electronics, Osaka, Japan). The suspensions of three different concentrations for each particle size were prepared by diluting with water, as listed in Table 1.

2. Experimental methods 2.3. Setup for detection of photoacoustic responses 2.1. Gold nanoparticles The aqueous suspensions of spherical gold NPs with different diameters (dp = 9.4, 19.9, 40.2, 49.3, and 59.9 nm at number concentrations of 5.7 × 1012 , 7.0 × 1011 , 9.0 × 1010 , 4.5 × 1010 , and 2.6 × 1010 particles/mL, respectively) were purchased from British BioCell International (Cardiff, UK). The concentrated suspensions were prepared in clean test tubes by solvent evaporation at 60 ◦ C [26]. Before and after this concentration procedure, no significant change was observed in the optical density (OD) spectra of the gold NP suspensions, indicating that the concentration procedure did not significantly affect the morphology and the monodispersity of the gold NPs. Thus, the suspensions of three different concentrations for each particle size were prepared, as listed in Table 1.

Fig. 1a shows our experimental setup for the PA signal detection, which is almost the same as employed in our previous studies [25–28], except for the laser device. A sample cuvette with a light-pass length of L = 0.92 mm was immersed in a temperaturecontrolled water bath with precision of ±0.1 ◦ C and illuminated by a pulsed beam from a tunable laser system with optical parametric oscillator (Opolette 355 II; OPOTEK, Carlsbad, CA, USA), which exhibited the pulse width of tL = 5 ns and the repetition rate of 20 Hz. The wavelength of this laser was set at ex = 560 nm, and the energy was I0 ≈ 100 ␮J/pulse. The beam diameter was reduced to 1.0 mm by a plano-convex lens with a focal length of 150 mm. Accordingly, the cross section of the specific region irradiated with the laser pulse was sL ≈ 0.785 mm2

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T. Fukasawa et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 487 (2015) 42–48

phological/physicochemical modifications of the gold NPs and the DiI-containing PS NPs. 3. Theoretical descriptions 3.1. Pressure pulse from a heated monodispersed suspension containing particles

Fig. 1. (a) Illustration of the experimental setup. BS—beam splitter, PD—photodiode, PC—computer. (b) Schematic representation of the monodispersed particle suspension before/after laser irradiation (see also Fig. S10). For more details, see the text.

and the laser fluence was F0 ≡ I0 /sL ≈ 127 J/(m2 pulse), which is sufficiently lower than the threshold fluence of the bubble formation around NPs, 500–1000 J/(m2 pulse) [29–41]. It is noted that the different laser system employed in our previous studies had tL = 0.8 ns, the repetition rate of 5 Hz, I0 ≈ 107 ␮J/pulse, sL ≈ 0.524 mm2 , and F0 ≈ 204 J/(m2 pulse) [25–28]. The acoustic signal from the laser-irradiated suspension was detected by an unfocused membrane-type hydrophone (H9C; Toray Engineering, Japan) with a measurable frequency range of 0.5–10 MHz. The distance between the hydrophone and the center of the sample cuvette was ≈38 mm. Prior to a series of measurements, the positions and angles of the hydrophone and the sample cuvette holder were carefully adjusted for maximizing signal intensity of the standard sample (e.g., an aqueous suspension of 40-nm gold spheres). The output signal from the hydrophone was recorded by an oscilloscope (TDS-2012; Tektronix, Beaverton, OR, USA) through two preamplifiers (Model 5682; Olympus NDT, Waltham, MA, USA) with a measurable frequency range of 0.5–31 MHz. The split laser beam was detected by a photo-diode (DET10A; Thorlabs, Newton, NJ, USA) and fed to the oscilloscope as the trigger signal. The acoustic signal was averaged over 128 pulses to reduce the noise. The acoustic wave stored in the oscilloscope was transferred to a computer via a USB port using the software (National Instruments LabVIEW SignalExpressTM Tektronix Edition). The PA signal was never processed before the data analysis. As long as the adjusted configuration of the hydrophone and the sample cuvette holder remains fixed throughout a series of measurements, no calibration is necessary for a comparison among the obtained PA responses; this is the case for the present study. If the configuration is readjusted, one should use the PA signal amplitude of the same standard sample at each configuration for calibration. The measurements were performed for the suspensions of the gold NPs or the DiI-containing PS NPs with different diameters at three different concentrations and temperatures (Tinit = 4, 20, and 37 ◦ C), as listed in Table 1. The PA signal profiles obtained are shown in Figs. S1–S9 of Supplementary data, where every waveform was hardly influenced by the material, size, and concentration of the NPs as well as the temperature. The OD spectra of these laser-irradiated suspensions were then measured. There was no significant difference between two spectra of every suspension before and after the laser irradiation, implying that the laser irradiation caused no mor-

Fig. 1b depicts the monodispersed particle suspension before/after laser irradiation. In the present study, we consider the case of low laser fluence, where the PA pressure pulse observed from a laser-irradiated suspension containing NPs increases linearly with the laser fluence [29–34]. If the laser fluence exceeds a threshold, the PA pressure pulse experiences a sharp nonlinear increase, where the water layer adjacent to the heated NPs undergoes a phase transition from liquid to vapor [29–41]; this is out of our scope in the present study. A heated monodispersed suspension containing particles at the number density of np is considered as in Fig. 1b (see also Fig. S10 of Supplementary data), where every particle has the thermal energy therein (ep ) and the surrounding liquid medium has the energy resulting from the heat conduction from the particle thereto (em ) immediately after the laser irradiation with a nanosecond pulse. The total thermal energy per particle is represented by etot ≡ ep + em . The physical properties of the particle and medium are defined as follows: ci , the specific heat capacity; i , the mass density; i , the isothermal compressibility; ˇi , the thermal coefficient of volume expansion, where the subscript i denotes the particle (p) or the medium (m). Hereafter, these properties are assumed to remain the constant values at the initial temperature (Tinit ), as listed in Table S2. Starting from the thermodynamic relation (V/V = − P + ˇ T, where V, P, and T denote the volume, pressure, and temperature changes of a system of interest, respectively), we have derived the local pressure rise ptot of the particle suspension upon short-pulsed laser irradiation as well as two contributions from the particles (pp ) and the medium (pm ), as elaborated in Ref. [26]:



ptot = np etot ×

 pp ≡

p p m





p p m







× x + m × (1 − x) = pp + pm



× np etot x



pm ≡ m × np etot (1 − x)

(1a)

(1b) (1c)

with i ≡ x≡

ˇi i ci i

ep em ,1 − x ≡ etot etot

(2) (3)

where  i denotes the Grüneisen parameter for the particle (i = p) or medium (i = m) and np etot represents the thermal energy of the particle suspension by optical-to-thermal conversion. It is worth noting that Eq. (1) is consistent with the idea given in Ref. [24]: If the pressure is measured in the medium far from the particle suspension, the contributions from the solid particle and the liquid environment can be separated by setting the liquid and the solid volume expansion coefficients, respectively, to zero. Once the time at an instant of thermal-to-acoustic conversion (tconv ) is assumed properly, we can straightforward estimate the acoustic pressure pulse in the absence of laser and sound attenuation, using Eq. (1) with the values of ei (t) (i = tot, p, m) at t = tconv . The time variations of the thermal energies per particle, ei (t), are calculated from Eq. (10) of Ref. [25] with the temperature profile of T(r,t) that is obtained by solving numerically the heat transfer

T. Fukasawa et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 487 (2015) 42–48

The OD value at wavelength  for the monodispersed suspension of particles in the cuvette of the light pass length of L is defined as OD ≡ −log10



I0

=

I ≡ I0 exp −np ext L



np ext L loge 10

(4) (5)

I0 ≡ sL F0

(6)

where sL and F0 are the cross section and the optical fluence of incident light, respectively. The extinction cross-section of the particle ( ext ) is given by ext ≡ abs + sca

(7)

where  abs and  sca are the absorption and scattering crosssections, respectively. In contrast, the absorbance is defined as A ≡

np abs L loge 10

(8)

which should be equal to Eq. (4) only if the scattering is negligibly small (i.e.,  sca   abs ). The thermal energy generated by a laser-irradiated particle is given by e0 ≡ th abs F0

(9)

where  abs F0 denotes the optical energy absorbed per particle and th is the ratio of the thermal energy generated to the optical energy absorbed. According to Refs. [43,44], th is represented by th

( ex − ¯ em ) = (1 − ˚PL ) + ˚PL =1−

ex



ex ¯ em 

ap = C=

abs ext F0 loge 10 L

0.1 0 400

500 600 700 Wavelength (nm)

where C is an apparatus constant. A measure of the PA pressure pulse is then given by ptot ptot = Cap th × OD np e0

(14)

Eq. (14) is useful for analyzing the PA pressure pulses observed from the particle suspensions of different particle sizes and concentrations, as will be shown in Section 4.3.

4. Results and discussion 4.1. Optical density spectra of nanoparticle suspensions Fig. 2 shows the OD spectra for suspensions of Au-60 and PS-63 measured with a UV–vis spectrophotometer (UV-1800; SHIMADZU, Kyoto, Japan). The OD spectrum of Au-60 had a peak at  = 532 nm due to the surface plasmon resonance of the gold NPs in water. On the other hand, the OD spectrum of PS-63 exhibited the first and second peaks at  = 554 and 520 nm, respectively, which originated from the chromophore of DiI dyes. As explained in Section 2.3, the wavelength of the nanosecond laser pulses for the PA signal measurements was set at ex = 560 nm, which was close to the maximum optical density wavelengths of these NP suspensions.



˚PL

(10)

where ˚PL is the photoluminescence quantum yield defined as the ratio of the number of photons emitted to the number of photons absorbed, ex the frequency of the exciting radiation (corresponding wavelength, ex ), and ¯ em the mean frequency of the ¯ em ). A nonluminescence emission (corresponding wavelength,  luminescent particle should exhibit ˚PL = 0 and th = 1. A combination of Eqs. (4) and (9) gives the relationship between the thermal energy (np e0 ) and the optical energy (OD ) of the particle suspension: np e0 = Cap th × OD

0.2

Fig. 2. Optical density spectra of an Au-60 suspension (dashed line) and a PS-63 suspension (solid line), which were measured using cuvettes with the light path length of L = 0.92 mm.

3.2. Relationship between optical density and thermal energy of a particle suspension

I

0.3

Optical density (-)

equations for a spherical particle and its surrounding medium (i.e., Eqs. (4)–(6), (8), (9) of Ref. [25]), where r denotes the distance from the center of the spherical particle. Following Egerev et al. [42], tconv was assumed to be the time for the end of laser irradiation, namely tconv = tL (=5 ns) in the present phenomenological modeling, where the time variation of the light intensity was represented by a rectangular profile with the full width at half maximum (tL ). It is worth noting that the thermal expansion coefficient of water at 4 ◦ C is zero, ˇwater = 0, as in Table S2. At the ambient water temperature of 4 ◦ C, Eq. (1) gives ptot = pp and pm = 0, suggesting that the acoustic pressure pulse at 4 ◦ C is never contributed by the heat within the water medium, but solely by the heat within the particles. It is therefore important to compare between the experimental results and the theoretical estimations at this temperature point.

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(11) (12) (13)

Fig. 3. (a) The spatial distribution of the temperature rise, T(r, t), around a spherical 60-nm NP of gold (dashed line) and PS (solid line) in water at 20 ◦ C after t = tL = 5 ns. The temperature rise was normalized by Tref ≡ e0 /(cm m vp ), where e0 represents the thermal energy generated inside a particle of volume vp due to the laser irradiation. The inset shows the magnification of the medium region next to the particle surface. (b) The ratio of the thermal energy remained inside the NP to the total thermal energy, ep /etot , for a spherical NP of gold (dashed line) and PS (solid line) in water at 20 ◦ C after t = tL = 5 ns, as a function of the NP diameter. Almost the same simulation results were obtained for the temperature profiles and thermal energy ratios at different temperatures of 4 and 37 ◦ C.

T. Fukasawa et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 487 (2015) 42–48

Peak signal normalized by OD560 (a.u.)

46

2.0

(a)

0.8

1.5

0.6

1.0

0.4

0.5

0.2

0 0

20

40

0 60 80 60 70 80 Particle diameter dp (nm)

(b)

90 100

Fig. 4. The normalized peak value of PA signals from an NP suspension at 4 ◦ C (triangle), 20 ◦ C (diamond), and 37 ◦ C (circle), as a function of the NP diameter dp : (a) gold and (b) PS. The data collected from the NP suspensions of three different concentrations (see Table 1) were expressed as the mean ± standard error of mean.

Fig. 5. The calculated acoustic pressure pulse ptot from a laser-irradiated NP suspension of gold (a) and PS (b) as a function of particle diameter dp at 4 ◦ C (dotted line), 20 ◦ C (dashed line), and 37 ◦ C (solid line). Every value of ptot was normalized as (ap th ) (ptot /np e0 ), which corresponds to the experimental PA signal (ptot /OD560 ) shown in Fig. 4.

4.2. Theoretical estimation of temperatures and thermal energies

expressed as the mean ± standard error of mean. This normalized peak value of the PA signal is equivalent to ptot /OD560 and should be constant for a given diameter of NP (dp ) irrespective of OD560 or the NP concentration (np ), according to Eq. (14) with Eq. (1a). This is the case for Fig. 4, though some scatters were observed around a few points: this result demonstrates the accuracy of our experimental observation as well as the validity of our phenomenological modeling. As shown in Fig. 4a, the normalized peak values of the PA signals from gold NPs at 20 and 37 ◦ C decreased with dp , where the latter (at 37 ◦ C) was larger than the former (at 20 ◦ C) in the size range of dp < 60 nm. In contrast, the normalized peak signal from the gold NPs at 4 ◦ C increased slightly with dp and was significantly smaller than those measured at 20 and 37 ◦ C. In the case of PS NPs shown in Fig. 4b, the normalized peak signal at every temperature appeared to be almost constant in the size range of dp < 80 nm and then increased gradually with dp . This particle-size dependence of PA response from a PS suspension was theoretically predicted in Ref. [45]. For a given NP diameter of PS, the normalized peak signal increased with increasing temperature. Similar particle-size dependence of PA response has been reported for the other types of dye-containing polymer NPs composed of poly(methyl methacrylate), poly(ethyl methacrylate), poly(n-butyl methacrylate), and poly(iso-butyl methacrylate) as well as PS [27]. Eq. (14) indicate that the experimental PA signal (ptot /OD560 ) corresponds to the calculated pressure pulse (ap th ptot /np e0 ), apart from an apparatus constant C. Fig. 5 shows the calculated pressure pulse from an NP suspension of gold and PS as a function of dp (≤100 nm) at three different temperatures, where the physicochemical properties in Tables S2 and S3 and Fig. S11 were employed. A comparison between Figs. 4 and 5 demonstrates that the size and temperature dependencies of the theoretical estimations were in agreement with those of the experimental results for the gold NPs as well as the PS NPs. Using the physical properties of gold, PS, and water listed in Table S2 (see the dimensionless prefactors), we can rewrite Eq. (1) with etot = e0 as

Fig. 3a displays the simulation results of the spatial distribution of the temperature rise around a 60-nm NP of gold and PS at 20 ◦ C immediately after the laser irradiation (i.e., t = tL = 5 ns), when the temperature of the NPs became maximal. The temperature profile inside the 60-nm gold NP was almost homogeneous. This is due to the large thermal diffusivity of gold, p (≡kp /cp p ) = 1.27 × 10−4 m2 /s; indeed, the thermal diffusion distance of gold for the laser pulse duration is calculated as (p tL )1/2 = 797 nm, which is at least 27 times larger than the radii of gold NPs employed in the present study (rp < 30 nm). On the other hand, the temperature profile inside the 60-nm PS NP was inhomogeneous to exhibit the lager values at the more central positions. This is because the thermal diffusivity of PS is small (p = 8.57 × 10−8 m2 /s) so that the thermal diffusion distance of PS for the laser pulse duration, (p tL )1/2 = 20.7 nm, is smaller than the radii of PS NPs employed in the present study (rp > 30 nm). In spite of this difference in temperature profile inside the 60-nm particle between gold and PS, the temperature profile of water around the gold NP was almost the same as that around the PS NP, where the normalized temperature rise of water in the vicinity of the gold NP was slightly larger than that of the PS NP (see the inset of Fig. 3a). Similar temperature profiles inside/outside the particles were obtained for the gold and the PS NPs of dp ≤ 100 nm. Fig. 3b shows the simulation results for the ratio of the thermal energy inside the NP to the total thermal energy, ep /etot , for a spherical NP of gold and PS in water at 20 ◦ C after t = tL = 5 ns, as a function of the NP diameter. The fraction of the thermal energy inside the NP increased with increasing NP diameter for both gold and PS NPs. This is because the heat was generated by the optical power deposition to the NP and more slowly transferred from the larger NP to the surrounding medium. The fraction of the thermal energy inside the PS NP was larger than that inside the gold NP for every diameter. This is explained by the thermal diffusivity of PS significantly smaller than that of gold, as mentioned above (see also Table S2). At temperatures of 4 and 37 ◦ C, we obtained almost the same results as those at 20 ◦ C shown in Fig. 3. 4.3. Comparison between experimental results and theoretical estimations Fig. 4 displays the experimental PA signals from the NP suspensions of gold and PS as a function of the NP diameter at three different temperatures, where every peak value of the PA signal was normalized by the optical density of the NP suspension (OD560 ). The data collected from the NP suspension of three different concentrations (see Table 1 and Figs. S1–S9 of Supplementary data) were

⎧ 0.038x ⎪ ⎨

ptot = −0.070x + 0.108 np e0 ⎪ ⎩ −0.153x + 0.191

at 4◦ C at 20◦ C at

(15)

37◦ C

for the gold NPs and

⎧ 0.324x ⎪ ⎨

ptot = 0.216x + 0.108 np e0 ⎪ ⎩ 0.133x + 0.191

at 4◦ C at 20◦ C at 37◦ C

(16)

T. Fukasawa et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 487 (2015) 42–48

for the PS NPs, where x monotonically increases from zero to unity with increasing dp (see Fig. 3b). The increase of the Grüneisen parameter for water medium with temperature (i.e.,  m = 0, 0.108, and 0.191 at 4, 20, and 37 ◦ C, respectively) explains the temperature dependence of the experimental results shown in Fig. 4. The negative sign of the prefactor for x in Eq. (15) for an NP suspension of gold at 20 and 37 ◦ C elucidates the monotonic decrease of the normalized pressure pulse with NP size (see Figs. 4a and 5a). In contrast, the positive sign of the prefactor for x in Eq. (15) at 4 ◦ C clarifies the monotonic increase of the normalized pressure pulse with NP size. It should be noted that ap of gold NPs with dp ≤ 100 nm hardly influences the normalized pressure pulse defined by Eq. (14), because it decreases slightly with NP size (see Fig. S11). In the case of PS NPs, on the other hand, the positive sign of the prefactor for x in Eq. (16) explains the monotonic increase of the normalized pressure pulse with NP size (see Figs. 4b and 5b). 4.4. Strategy on how to design nanoparticles for photoacoustic contrast imaging In the case of low-level laser irradiation, our phenomenological model for acoustic pressure pulse from a laser-irradiated particle suspension is based on the thermodynamic relation with the numerical solutions of the heat transfer equations (i.e., Eq. (1) with Fig. 3b), where no cavitation is assumed to occur in the particle suspension and the acoustic pressure pulse is represented by a sum of two contributions from the particles and the medium. It successfully explains the size and temperature dependencies of the acoustic pressure from a laser-irradiated particle suspension of gold and PS in water, as demonstrated in Section 4.3. Consequently, the particle-size dependence of the PA response from a particle suspension is determined by the physical properties of material composing the particles: (i) in the case of p  p /m >  m (e.g., the particle suspensions of PS in water at ambient temperatures and of gold at 4–9 ◦ C), the contribution of acoustic pressure from the particles is larger than that from the medium and the magnitude of PA response increases with particle size; (ii) in the case of p  p /m <  m (e.g., the particle suspensions of gold in water at the ambient temperatures above 9 ◦ C), the contribution of acoustic pressure from the particle is smaller than that from the medium and the magnitude of PA response decreases with particle size. This finding gives us a strategy for fabrication of particles for PA contrast imaging at low laser fluence. For an example, let us consider how to enhance the PA contrast in a human body at 37 ◦ C. On the condition that the mass accumulation of the contrast agent particles on a target is kept constant, the material and the size of the particles should be tuned with each other in the following way: (i) the larger particles of polymers such as PS are preferable, because the contribution of acoustic pressure from the particles is larger than that from the medium; (ii) the smaller particles of metals such as gold are more favorable, because the contribution of acoustic pressure from the particles is smaller than that from the medium. Thus, the results from our phenomenological model help us design the particles for PA contrast imaging at low laser fluence, though their optical absorption efficiency as well as their accumulation efficiency to a target should be also taken into account. Additionally, our phenomenological model allows us to discuss the effect of surface modification of particles on the PA response, from the viewpoint of the heat transfer from a particle to its surrounding medium. Surface modification of gold particles (e.g., silica coating [46], polymer coating [47], and ligand addition [48,49]) changes the interfacial heat conduction from the particle to its surrounding medium. Indeed, Chen et al. have demonstrated that the PA signal intensity of silica-coated gold nanorods [23] and nanospheres [24] is enhanced by the presence of silica shells at ambient temperature, and have concluded the increment in the

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PA signal intensity is attributable to the enhancement of the interfacial heat conduction from the gold core to the water medium due to the presence of the silica shell. These results are consistent with the estimation from our phenomenological model: The aqueous suspension of gold NPs at ambient temperature gives p  p /m <  m , where the contribution of acoustic pressure from the water medium is larger than that from the gold NPs, and the enhancement of thermal diffusion by the presence of the silica shell around the gold NP results in the increment of PA signal intensity. 5. Conclusions We carried out the experimental measurements of the PA responses, where the suspensions of spherical gold NPs (dp = 9.4, 19.9, 40.2, 49.3, and 59.9 nm) and dye-containing spherical PS NPs (dp = 63.1, 73.0, 85.9, and 93.7 nm) in water at different NP concentrations and temperatures (4, 20, and 37 ◦ C) were irradiated with nanosecond laser pulses at low laser fluence. In the case of the gold NPs at 20 and 37 ◦ C, the PA signal normalized by the optical density of the suspension decreased with increasing NP size, dp . In contrast, the normalized PA signal of the gold NPs at 4 ◦ C increased slightly with dp and was significantly smaller than those measured at 20 and 37 ◦ C. On the other hand, the normalized PA signal from the suspension of the PS NPs at each temperature gradually increased with dp . For a given NP diameter of both gold and PS, the normalized PA signal from the suspension increased with increasing temperature. The dependencies of the PA responses on the material and size of NPs as well as the temperature were explained by our phenomenological model, where the acoustic pressure pulse was represented by a sum of two contributions from the NPs and the surrounding medium. These results suggest that the acoustic pressure pulses from a laser-irradiated NP suspension are influenced by the physicochemical properties of the NPs and the surrounding medium. The findings of the present study and our phenomenological model provide a strategy on how to design NPs for photoacoustic contrast imaging. Acknowledgements This work was partly supported by the Innovative Techno-Hub for Integrated Medical Bio-imaging of the Project for Developing Innovation Systems, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.colsurfa.2015.09. 051. References [1] M.A. Hahn, A.K. Singh, P. Sharma, S.C. Brown, B.M. Moudgil, Nanoparticles as contrast agents for in-vivo bioimaging: current status and future perspectives, Anal. Bioanal. Chem. 399 (2010) 3–27. [2] G.P. Luke, D. Yeager, S.Y. Emelianov, Biomedical applications of photoacoustic imaging with exogenous contrast agents, Ann. Biomed. Eng. 40 (2012) 422–437. [3] L.V. Wang, S. Hu, Photoacoustic tomography: in vivo imaging from organelles to organs, Science 335 (2012) 1458–1462. [4] D. Pan, B. Kim, L.H.V. Wang, G.M. Lanza, A brief account of nanoparticle contrast agents for photoacoustic imaging, wires, Nanomed. Nanobiotechnol. 5 (2013) 517–543. [5] D. Wu, L. Huang, M.S. Jiang, H.B. Jiang, Contrast agents for photoacoustic and thermoacoustic imaging: a review, Int. J. Mol. Sci. 15 (2014) 23616–23639. [6] V.P. Zharov, E.I. Galanzha, E.V. Shashkov, J.W. Kim, N.G. Khlebtsov, V.V. Tuchin, Photoacoustic flow cytometry: principle and application for real-time detection of circulating single nanoparticles, pathogens, and contrast dyes in vivo, J. Biomed. Opt. 12 (2007) 051503.

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