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Laser-induced generation of vapor bubbles in water around plasmonic nanoparticles was experimentally studied by optical scattering methods. Nanoparticle-generated bubbles spatially localize a laser-induced thermal field and also amplify the optical scattering relatively to that by gold nanoparticles. Bubble lifetimes and threshold fluencies were determined as functions of the parameters of a laser (pulse duration, fluence, interpulse interval), nanoparticle (size, shape, aggregation state), and of the sample chamber so as to optimize the conditions of bubble generation around plasmonic nanoparticles. Nanoparticle-generated bubbles are suggested as nano-sized optical sensors and sources of localized thermal and mechanical impact.
©2009 Optical Society of America
1. Introduction
Compared to any molecular optical absorbers, metal nanoparticles (NP) are the best optical-to-thermal energy converters due to their plasmonic properties and also are characterized by the highest photo- and thermal stability. These features of NPs have stimulated their increasing photothermal (PT) application in industry [1–5] and biomedicine [6–14]. Laser-induced PT phenomena consists of the initial thermalization of NPs that, in turn, rapidly causes environmental thermal processes such as the heating of the surrounding media [2,11,15–19] (due to thermal diffusion), its vaporization (if the temperature exceeds the vaporization threshold), and the generation of acoustic and shock waves [20–22]. All these processes depend on the thermal energy generated by NP during plasmonic interaction with a laser pulse, whereas the distribution of the NP-generated energy between the above processes depends upon the laser pulse duration. Local vaporization around a NP still remains the most under-recognized PT phenomenon because its nano-scale nature complicates the analysis of bubble generation. However, the bubble mode of the PT interaction may localize laser-induced thermal and mechanical impacts around plasmonic NPs in space and time. Such localization cannot be achieved either with long or ultra-short laser pulses. Too long pulses (or continuous optical activation) cause the thermal field to spread over a large space (many orders of magnitude larger than the NP size) due to thermal diffusion. Ultra-short laser pulses concentrate the thermal field within the NP, but generate pressure waves that also spread over a large volume.
In contrast, a bubble may potentially concentrate the laser-induced thermal field and mechanical (pressure) impact around a NP with their characteristic size and duration determined by the bubble diameter (in the range of 50 – 1000 nm) and lifetime (in the range of 5 – 500 ns), respectively. These two parameters may be considered as the measures of the PT process in space and time and can be potentially controlled through the parameters of NPs and laser radiation. Furthermore, optical and acoustic means of bubble detection may help analyze and visualize nano-thermal processes. Controllable generation of bubbles and their quantitative detection and imaging may improve the existing PT applications of plasmonic NPs and stimulate new. For example, NP-generated vapor bubbles have already improved the selectivity and efficacy of PT therapy and diagnostics [23–25] and of some chemical processes [26]. The well-known excellent optical scattering properties of bubbles [27–35] may help in their detection at nano-scale and potentially improve the NP-based optical sensing and imaging.
Optical generation and detection of vapor bubbles was studied on a macro- and micro-scales theoretically [36–44] and experimentally for different biomedical [20, 34, 45–53] and technical [54–62] tasks. However, the studies of the bubble generation around laser-heated plasmonic NPs [63–66] or on a nano-scale [34] are rather scarce. Furthermore, the macro-mechanisms of bubble generation cannot be directly downscaled to describe the NP-generated vapor bubbles. For example, for micro- and macro-absorbers the threshold laser fluence of bubble generation increases with an increase in the particle size [36, 67]. For NPs this trend is the opposite one: the bigger the size of plasmonic NPs, the lower is the fluence threshold for bubble generation [68, 69]. In this work we have experimentally studied the processes of PT generation and detection of vapor bubbles around plasmonic gold NPs. We have focused on optimization of the parameters of laser pulses, NPs, and surrounding media for the most efficient generation of localized vapor bubbles around NPs. The existing models of NP-generated bubbles [63, 70, 71] fail to take into account all involved processes including the NP absorbance cross-section and stability at extreme temperatures [72–78], the influence of a bubble on a laser pulse, etc., so the experimental approach is still more realistic. In order to underline the thermal origin of such bubbles, we define them as photothermal bubbles (PTB).
2. Methods and materials
2.1 Bubble generation
We consider that vaporization of the medium around a NP involves several processes. Laser pulse-induced thermalization of a NP occurs in approximately 1 ps [15, 78–80], and the temperature of the NP may reach or even exceed its melting point (1337 K for gold). Next, thermal diffusion from a NP to adjoining medium delivers the thermal energy required for its vaporization. Formation of a thin vapor layer around a NP creates a PTB nucleus. The PTB develops from a nucleus provided that a sufficient initial potential energy was deposited for overcoming the opposing forces of the surface tension and viscosity. After the emergence of the bubble it undergoes expansion to a maximal diameter and then collapses. The bubble lifetime may be considered as linearly proportional to its maximal diameter [38, 42, 45, 81–84]. The minimal fluence of a single laser pulse that provides bubble generation is defined as the PTB threshold fluence. While the mechanism of the bubble evolution is well studied, the transition from the exposure of a NP to a laser pulse to the nucleation and expansion of PTB is less understood. However, we can estimate spatial and temporal conditions of the ingress of thermal energy into the nano-volume around a NP. If the localization of a PT impact is required, there should be no pressure and shock waves, and also the thermal diffusion losses should be minimized. The conditions for the generation of pressure waves and for thermal diffusion can be expressed in terms of the diameter Dnp of the NP via the acoustic, τa = Dnp/cg, and thermal, τt = Dnp 2/ 24a, relaxation times, respectively, where cg is the speed of sound in the NP, and a is the thermal conductivity of the surrounding medium (Fig. 1).
When the optical pulse duration τl>τa, no pressure or shock wave would emerge. Next, when τl<τt, the losses due to thermal diffusion are negligible, and the entire heat released is concentrated in a small volume around the heat source. Thus, we may classify the PT processes around a plasmonic NP in terms of the laser pulse duration and diameter of the NP as micro-thermal, nanothermal (with bubbles) and nanothermal without bubbles (Fig. 1). In many cases NPs may aggregate into a cluster [85–86] which acts as a solid thermal source of a much bigger diameter than a single NP. The gray area in Fig. 1 shows the optimal conditions of local heating of the medium around a NP: minimal heat losses and no pressure waves. In this case the energy released is efficiently used for local heating and vaporization. This approach is very schematic but still shows the applicability of available lasers and NPs.
In our work we have employed a pulse of length 10 ns, 532 nm (Nd-Yag LS2132, Lotis TII, Minsk) and a much shorter subnanosecond pulse of 0.5 ns and at the same wavelength (STA-01 SH, Standa Ltd, Vilnius). Two pumping laser beams were directed into the illumination path of an inverted optical microscope (Nikon 200) and were identically focused into the sample chamber with a water suspension of gold NPs (Fig. 2). The pulse fluence was varied by rotating the Glan prism and was measured using an Ophir PE10-SH energy meter (Ophir Optronics, Ltd., Israel) and an image detector (Luca DL-658M, Andor Technology, Ireland). The latter provided imaging and direct measurement of the actual diameter of the laser beam. A NP sample was irradiated at several different locations one by one with a single focused laser pulse (diameter 7.0 μm) of the same fluence by scanning the sample on the microscope stage. The concentration of the NPs was adjusted so as to avoid the overlapping of the laser induced thermal fields with the bubbles. Such a setup has ensured that a single NP and a single event were studied.
Fig. 1. Classification of the photothermal processes generated by plasmonic nanoparticles due to optical absorption of laser pulse and follow-up thermalization of the nanoparticle. Bubble mode is shown in light gray. Shift of the border between bubble mode and pressure wave mode due to increase of the nanoparticle temperature during plasmonic interaction is hatched.
2.2 Bubble detection
We used two optical detection methods that take advantage of the excellent optical scattering properties of bubbles. A bubble can also be detected acoustically, but for nano-sized objects the optical methods provide a better space and time resolution. Also the PTB generated around a NP can be a single event as in the case of NP photodamage. The scattering imaging of vapor bubbles is a well-known method successfully applied for macro- and micro-sized bubbles [34,104,105]. We have adapted this method so as to allow the detection of NP-generated bubbles. The imaging of NPs and PTBs was realized by using side illumination of the NP sample with a pulsed probing laser beam at a wavelength (690 nm) different from the pumping laser wavelength (532 nm). A short probing pulse with duration 0.5 ns and with a tunable time delay relative to the pumping pulse provided time-resolved imaging of a short-living scattering object such as PTB (Fig. 2). Optical scattering is also used for the imaging of metal NPs and their clusters [87–94]. We may expect that the scattering from PTB would amplify the amplitude of the scattered light relative to that from NP, because the diameter of a PTB is larger. We have recently obtained the first experimental evidence of the amplification of optical scattering at a nanoscale by PTBs [35]. For quantitative analysis of the bubble-related images we have introduced the relative scattering amplitude Ssc(t)=[I(t) - Ib]/[I(0) - Ib] that describes the pixel image amplitude I(t) of optical scattering by a PTB relative to that by a NP I(0) (Ib is the average pixel image amplitude of the background).
Fig. 2. Experimental setup: single gold NPs in water were placed in the sample chamber mounted on the microscope stage; PTB generation was provided by focused single pulses (532 nm, 05 ns or 10 ns); a pulsed probing laser (690 nm, 05 ns) provided time-resolved optical scattering imaging of PTB and a continuous probing laser (633 nm, 1 mW) provided the monitoring of the integral optical scattering of PTBs.
While allowing to “see” the PTB the pulsed imaging can hardly provide kinetic measurement. The latter was realized by the thermal lens method [95, 96] in a response mode. An additional continuous probing beam (633 nm) was directed to the sample and focused on it collinearly with pumping laser beams (Fig. 2) and its axial intensity was monitored by a high-speed photodetector (PDA10A, Thorlabs Inc.) and 200-MHz USB digitizer (Bordo 424, Auris, Minsk). The PTB-induced scattering of a part of the probing beam decreased its axial amplitude resulting in a dip-shaped output signal. This method also allows the detection of acoustic waves and thermal field as they create local gradients of the refractive index in the beam path. The response mode allowed measurement of the PTB lifetime that characterizes a maximal diameter of the bubble. Image and response modes were used simultaneously thus combining the imaging and measuring of the lifetime. The PTB-related optical signal can be detected from a zero level when the light scattered by the PTB in the specific direction is registered and thus produces the positive signal that characterizes the angle-specific scattering effect. Alternatively, the probing beam can be directed into the sensor thus producing some base-level signal. The scattering by the PTB in all directions would decrease the amount of light at the detector thus producing the negative signal that characterizes the integral scattering effect. Also, besides the pulsed probing beam the continuous illumination and detection can be used so to register a kinetical behavior of the PTB. We defined the continuous optical monitoring of the PTB as a response mode and the time-resolved pulsed imaging of the PTB as an image mode.
2.3 Samples
Several types of gold NPs and their clusters were used as plasmonic heat sources: spherical gold NPs with diameters of 30 nm and 100 nm (a plasmon resonance peak at 530 nm), gold nanorods 14 nm×45 nm (plasmon resonance peaks at 532 nm and 750 nm). All samples were studied as water suspensions in closed microvolumes confined to a glass sample chamber with a diameter of 9 mm and variable height from 10 μm to 1000 μm. The concentration of NPs was adjusted so as to provide a mean interparticle distance of 8 μm. This prevented ensemble plasmonic and PT effects. In addition to single NPs we prepared their aggregates by adding 40% of acetone and resuspending NPs in water. We define the NP cluster as the aggregate with the interparticle distance smaller than the NP size and containing at least several NPs. Formation of clusters was verified by measuring the optical extinction spectra of NP suspensions (650 Red Tide Ocean Optics, Inc, Dunedin, FL) and by imaging samples in the side scattering mode using the above-mentioned experimental setup. It has been established that the optical extinction spectrum of a NP cluster broadens relative to that of a single NP. We studied this state of NPs, because in many applications (especially in biomedical ones) NPs form clusters.
Besides the NP samples, we studied PTB generation in optically absorbing micro-objects and in homogeneous absorbing solutions so that the PTB mechanisms be compared. We used 7-μm red blood cells (RBC) as microobjects with a uniformly distributed light-absorbing agent (hemoglobin, Hb). We also used a purified Hb solution as a homogeneous optical absorber obtained by a standard thawing method [97 ] from RBC. In both cases the whole irradiated volume is heated by a laser pulse and there is no any localized heat sources. Optical absorbance of the Hb solutions and RBC suspensions was verified by a spectrophotometer.
3. Results
3.1 Generation and detection of PT bubbles around gold NPs and their clusters
We exposed a sample with 30-nm gold spheres to single pumping laser pulses of 0.5-ns duration at gradually increasing fluence levels. All samples were studied in cuvettes of diameter 9 mm and height 10 μm. Optical scattering images were obtained prior to a pumping pulse (Fig. 3(a) and 3(c)) and at a specific time delay (9 ns) after the pumping pulse (Fig. 3(b) and (d)). Responses were obtained simultaneously (Fig. 4) with the pumping pulse. Without the pumping pulse the scattering from single NPs was too weak to form the detectible images of single NPs. However, application of single pumping laser pulses at the fluence starting from 0.5 – 0.6 J/cm2 resulted in the appearance of bright diffraction-limited spots in the images. Simultaneously detected responses yielded symmetrical dip-shaped signals (typical of PTBs) with durations starting from 15 ns (Fig. 4(a)). The PTB durations were experimentally measured as the widths of the dip-shaped signals at the level of 0.5 of their maximums. We have never observed either fusion or overlapping of PTBs, because NPs were sufficiently separated. This allows us to consider that isolated bubbles were generated and detected.
Fig. 3. Time-resolved optical scattering images obtained for: a) a suspension of 30-nm gold NPs (no pulse), b) 30-nm gold NP exposed to a single pump laser pulse (532 nm, 0.5 ns, 0.9 J/cm2), c) clusters of 30-nm gold NPs (no pulse), d) clusters of 30 nm gold NP exposed to a single pumping laser pulse (532 nm, 0.5 ns, 0.12 J/cm2), the images (b) an (d) were obtained with a 9-ns time delay relative to the pumping pulse. Space bar is equal to 6 μm.
Table 1. Parameters of NP-generated PTBs as measured in image and response modes for a single 0.5-ns laser pulse at 532 nm
Unlike the single NPs, their clusters have scattered the probing pulse much more strongly and have formed images (Fig. 3(c)). The increased optical scattering by NP clusters compared to that by single NPs was due to their increased size that was estimated at 400–500 nm by trans-illuminated imaging. Application of a single pumping laser pulse has caused bright spots in scattering images (Fig. 3(d)) that spatially coincided with the NP clusters. Pixel amplitudes of the images and the lifetime of cluster-generated PTBs were found to be significantly higher, and the threshold fluence of bubble generation significantly decreased compared to those for single NPs (Table 1). As can be seen from Fig. 3, the bubbles have amplified the optical scattering. This effect was characterized by the relative scattering amplitude (Table 1). The amplification effect was also stronger for the NP clusters than for single 30-nm NPs. The significant increase in the duration of the responses of the cluster-generated PTBs (Table 1, Fig. 4(b)) relative to that of single NPs (Fig. 4(a)) implies an increase in the maximal diameter of cluster-generated PTB and thus better explains the optical amplification, because optical scattering is very sensitive to the size of a scattering object.
We have measured the probabilities of the PTB detection in image and response modes as a function of laser fluence (after the exposure of 40 different zones to identical laser pulses) and thus have determined the threshold fluencies that corresponded to the probability values of 0.5. The probability of PTB detection in the image mode was found to be higher at lower fluencies than that measured with PTB responses and the image mode yielded the PTB threshold to be 0.088 J/cm2, while the response mode yielded the PTB threshold to be equal to 0.3 J/cm2 for the same sample (clusters of 30-nm NPs). Therefore, the sensitivity of PTB detection in an image mode is higher than in a response mode. All PTBs were mainly observed during the first pumping pulse. In the case of single NPs, we observed no PTB generation during repeated exposures of the same area of the sample. This could have been caused by the continuous motion of NPs in water or by their photodamage. In the case of optically detectible and stationary NP clusters, the PTBs were reproducible at the level of the pumping laser fluence close to the PTB generation threshold. However, at an increased pumping fluence the PTBs deteriorated within 4–8 pulses applied with a 1-3-s interval.
Based on the above results, we may conclude that the generation of PTB around NP has a threshold nature, that the PTB may be optically detected by scattering images and responses, and that the clusterization of NPs significantly improves the conditions of PTB generation by decreasing its threshold fluence and increasing its lifetime, and hence a maximal size. According to the images obtained, the PTB generated at the fluences close to the threshold and above it were of submicrometer size because they produced diffraction-limited images. Next, we have studied the PTB properties by analyzing their images and responses.
Fig. 4. Time responses for a single pumping pulse (532 nm, 0.5 ns): (a) PTB around 30-nm gold NP (0.9 J/cm2), (b) PTB around a cluster of 30-nm gold NPs (0.9 J/cm2), (c) thermal signal in the sample of 30-nm gold NPs at the fluence below the PTB threshold (0.5 J/cm2), (d) PTB and thermal signal in the sample with hemoglobin as a homogenous absorber; the insets in (c) and (d) show the relaxation of the bulk thermal signals at full time-scales (a delay between the zero time and the signals is the result of the offset caused by synchronization of the digital oscilloscope that was used for the registration of the response).
3.2. Time-resolved imaging of PTBs in pulsed scattering mode
The optical scattering power of a PTB depends on its diameter, which, in turn, depends on the pumping laser fluence. This basic property of PTBs was studied by analyzing the relative pixel image amplitude as a function of the laser fluence at several time-delays (3, 9 and 24.5 ns) of a probing pulse. The clusters of 30-nm NPs and the PTB generated around them were analyzed. The relative scattering amplitude is shown in Fig. 5(a) as a function of the pumping pulse fluence. We have found almost linear proportional dependences on the laser fluence (Fig. 5(a)) at all time-delays of the probing pulse. However, we have discovered apparent saturation of the scattering image amplitude at higher fluencies, with the saturation fluence level, the PTB detection thresholds, and the values of the relative scattering amplitudes being different for different time-delays (Fig. 5(b)). In terms of the PTB dynamics the delay time corresponds to the specific diameter of PTB. This explains the poor scattering by a PTB at the 3-ns delay, because its size was too small at this stage for efficient scattering. In contrast, a too long delay also does not improve the scattering efficacy. Therefore, a maximal scattering efficacy (and maximal sensitivity of imaging) requires optimization of the probing pulse delay, and in our case this was 9 ns with maximal relative pixel image amplitude Ssc (Fig.5 (b)). We have not detected the image amplitude saturation effect at the 3-ns delay, whereas at longer delays of 9 ns and 25 ns the saturation thresholds decreased to 0.6 J/cm2 and 0.25 J/cm2, respectively. We may conclude that the optimal delay time of the probing laser would provide maximal sensitivity of PTB imaging in the scattering mode.
Fig. 5. (a). Influence of the fluence of a single pumping laser pulse (0.5 ns, 532 nm) on the relative scattering amplitude Ssc(t) of the PTB generated around 30-nm NP clusters (solid squares) and corresponding PTB lifetime (NP clusters shown by hollow squares, single 30-nm NPs shown by hollow circles), the images were obtained at 9 ns time delay of probing pulse relatively to pumping pulse; (b) Influence of the time-delay of a probing laser pulse (0.5 ns, 690 nm) on the parameters of NP cluster-generated PTBs: relative scattering amplitude (black columns), PTB generation threshold (hollow columns) and scattering saturation threshold (gray columns).
3.3 PTB responses
Though the response mode is less sensitive than the image mode, it allows more flexibility, because it does not require precise localization of NPs and PTBs in the focal plane of the microscope objective. We used this mode to study the PTB lifetime (which also characterizes a maximal PTB size) as a function of the laser fluence and NP aggregation state (Fig. 5(a)). Both single NPs and their clusters generated PTBs starting from the specific threshold of the laser fluence (Fig. 5(a), Table 1). This fluence level was almost one order of magnitude lower for NP clusters relative to that for single NPs. This also means that clusters generate PTBs at a much lower initial laser-induced temperature, and therefore the clusterization of NPs significantly improves the efficacy of PTB generation. The clusterization of the NPs has decreases the fluence threshold of the PTB generation through several mechanisms. First, the ensemble of closely located NPs may enhance plasmon interactions thus producing more thermal energy than the equal number of separated NPs. At the same time we have found that NP clusterization rather broadens than shifts the plasmon spectra [25]. Secondly, the NP cluster accumulates much more thermal energy comparing to a single NP as the energy proportional to the volume of all NPs in the cluster. Next, the increase of the radius of the heat source (i.e. cluster vs a single NP) stimulates the bubble expansion by decreasing the two opposing hydrodynamical forces: the surface tension (that is inversely proportional to the radius) and the viscosity (that prevents the expansion of the vapor nucleus into the bubble for small radius in the case of a single NP). Thus the NP cluster would require lower optical fluence to generate the PTB. Besides, in biomedical applications a big single NP may not reach its target due to biological barriers that are accessible for smaller NPs assuming their clusterization after they pass such barriers.
The lifetimes of the PTBs at the threshold fluences were in the range from 15 to 25 ns and did not differ much for clusters and single NPs. This means that different heat sources produce similar minimal bubbles when the conditions of bubble generation approach the threshold. The shortest lifetime of PTB whatever the NP type, size, and state was about 15 ns. The difference between single NPs and their clusters became apparent with an increase in the laser fluence. The slope of the lifetime-fluence graph was much higher for clusters than for single NPs; furthermore, the clusters allowed generation of much bigger PTBs (with the lifetimes of several hundred ns) at relatively moderate levels of laser fluence (within 1 J/cm2), while almost no PTBs were detected around single NPs. Therefore, the clusterization of NPs improves also the selectivity of the PTB generation. It should be noted that the PTB lifetime almost linearly increased together with the pumping laser fluence and, unlike pixel image amplitudes, exhibited no signs of saturation (Fig. 5(a)). This implies that the above-reported saturation of the optical scattering signal may have an optical mechanism (possibly related to a limitation of light collection by the micro-objective) and that no saturation of the maximal diameter of PTB occurs during this effect.
A careful examination of the responses obtained for a NP suspension at laser fluence levels below the PTB threshold has revealed a weak thermal signal (Fig. 4(c)) that had a relatively sharp front (10–20 ns) and a long gradual tail of microsecond length (shown in the inset of Fig. 4(c) in full time scale). This signal describes the dynamics (heating and cooling) of the bulk thermal field induced due to thermal diffusion in the volume covered by the probing laser beam. A comparison of thermal responses (Fig. 4(c)) with the PTB responses (Fig. 4(a) and 4(b)) has revealed rather an important feature of the PTB mode: after the collapse of PTB the response amplitude returned to its baseline level, which indicates that the residual bulk temperature was the same as that prior to the pumping laser pulse. As can be seen from Fig. 4(c), a bulk temperature rise shifts the response from the baseline thus indicating the difference in the temperatures before and after exposure to the pumping laser pulse. However, we did not observe any residual heating of the medium after the PTB collapse (Fig. 4(a) and 4(b)) despite the increased pulse fluence. In the case of PTB generation the initial laser-induced temperature around the NP was higher than that induced by a lower fluence (Fig. 4(c)). Therefore the PTB may utilize almost the entire energy released by the NP, thus preventing any heating of the microenvironment outside the PTB and after its collapse. This partly corresponds to the results obtained with another type of optically absorbing NPs [26]. We also observed no phenomena that may utilize the PTB energy: the oscillation of bubbles which implies the effect of the viscosity of water, or the signals that can be attributed to pressure waves. To gain a better understanding of this result we have studied the PTB generation in a homogeneously absorbing solution without plasmonic NPs. The PTB’s response obtained (Fig. 4(d)) showed two superimposed processes: PTB and a bulk thermal field. A homogeneously absorbing medium is almost uniformly heated during the absorption of the laser pulse and this caused the combination of the PTB and thermal responses. In the case of a NP suspension the temperature field is highly nonuniform with a maximal temperature in the NP-adjacent volume where the PTB is generated. It may consume most of the thermal energy thus preventing the residual bulk heating. The explanation of the discovered “no-heating” phenomenon (comparing to the pronounced heating of the NP environment at the lower sub-threshold laser fluence) requires a further study of the NP-generated PTBs and may include the several mechanisms:
- the expanding bubble scatters the incident laser pulse thus reducing its fluence and the thermal energy accumulated by the NP, and the influence of this effect may increase for longer laser pulse;
- only a small fraction of the thermal energy of the NP is converted into the energy of the bubble (usually less than 1 %) and hence the dissipation of the PTB energy after its collapse does not cause a significant heating of the environment;
- the vapor inside the PTB prevents the heat transfer from heated NP into the environment outside the PTB thus creating the insulating effect due to almost adiabatic dynamics of the bubble;
- after the PTB collapse the bubble energy dissipates into the environment mainly as a heat, but also a small fraction of it may be converted into acoustical and optical emissions (sonoluminescence) though we have never observed these two effects in our experiments.
3.4. Influence of laser pulse duration and of the number of pulses
All of the foregoing results were obtained for the specific laser pulse duration (0.5 ns), NP type, NP size, and the size of the sample chamber. Next, we have examined the influence of the above parameters on PTB generation. The laser pulse duration was increased to 10 ns, while the wavelength and geometry were identical to those of the 0.5-ns pulse. Samples included gold spheres of the diameter increased to 100 nm, 14×45-nm gold rods, clusters of silica-gold shells (NS) with outer diameters of 60 and 170 nm and with broad extinction spectra. Finally, we measured PTB thresholds and lifetimes as a function of the sample chamber height. All experiments were performed in a response mode for a single laser pulse.
A 20-fold increase of the laser pulse length caused an increase in the PTB generation threshold fluence in all the NPs and their clusters studied (Fig. 6(a)). The PTB threshold ratio for 10 ns/0.5 ns pulses varied in the range from 13 (single 30-nm NPs) to 24 (single 100-nm NPs). This means that despite the significantly decreased intensity of the long laser pulse the efficacy of the PTB generation turned out to be relatively small. This could be due to the increased thermal losses in the case of the long pulse, as shown in Fig. 1. It may also be possible that PTB scatters the incident long pulse thus decreasing its actual fluence. As can be seen from Fig. 6(b), the PTB lifetimes for short and long laser pulses were almost equal at the threshold fluences, and thus the increase in the pulse length did not influence the maximal diameters of the PT bubbles. The reproducibility of the PTB was also the same for short pulses - the PTBs were not reproducible for single NPs and exhibited rapid deterioration when being generated around NP clusters.
Next, we compared different types of NPs and their clusters. The increase of the NP sphere diameter from 30 nm to 100 nm resulted in a several-fold decrease on the PTB threshold fluence. Even a stronger effect was discovered for gold nanorods despite the fact that 532 nm band does not provide maximal optical absorbance for this type of NPs. Minimal thresholds were achieved with NP clusters regardless the type of the NP (spheres and two different types of shells). We have found that an increase of the cluster size (estimated with the aid of an optical microscope) lowered the PTB threshold. Gold 60-nm nanoshell clusters of 500 — 700 nm yielded the lowest PTB threshold fluence of 12mJ/cm2. That sample also exhibited the best reproducibility of PTBs during repeated exposure of one cluster to the several laser pulses that were applied with 1 — 5-s intervals. Therefore, NP clusters may be considered as the best solution for minimizing the vaporization thresholds fluence and temperature.
Fig. 6. PTB generation threshold fluence (a) and lifetime at the threshold fluence (b) for single 30-nm gold spheres (NP30), gold rods 14 × 45 nm (NR), 100-nm gold spheres (NP100), and clusters of 30-nm spheres (cNP30), 170-nm gold shells (cNS170), 60-nm gold shells (cNS60) and for micro- and macroabsorbers: red blood cells (RBC) and a homogeneous hemoglobin solution (Hb). Black columns, 0.5-ns pulse; hollow columns, 10-ns pulse at 532 nm.
As the PTB lifetime is much longer than the duration of a short laser pulse, it may be interesting to compare the effect exerted by a pulse train with that made by a single pulse. We exposed single 30-nm NPs to paired short pulses with a variable interval: 1 ns and 6.5 ns. For an interval of 6.5 ns two pulses did not influence the threshold fluence levels and the lifetime of PTB. Thermal relaxation of NPs may occur before the arrival of the second pulse, therefore in terms of the PTB generation such a mode is equal to the single-pulse mode. At a shorter interval of 1 ns the PTB threshold decreased by a factor of 1.7 and the PTB lifetime increased by 1.5 times relative to the values obtained with a single pulse. Therefore the pulse train mode may additionally increase the efficacy of the PTB generation and may also lead to a decrease in the initial laser-induced temperature of a NP.
The next evaluated parameter was the height of the sample chamber (which was between two parallel glasses). We increased it from 10 μm to 120 μm and 1000 μm and measured the PTB threshold fluence and lifetime for single 30-nm gold spheres (Fig. 7). The increase of the cuvette height significantly lowered the threshold fluence of the PTBs’, but exerted almost no influence on their lifetime. As we used the cuvette with a closed volume (confined between two parallel glasses of the microscope slide and cover slip), the discovered effect may indicate the influence of a local pressure. This might have been caused by the generation and reflection of pressure and rarefaction waves by heated NPs. A detailed analysis of this effect is beyond the scope of the present work, however, we may conclude that a larger space inside the sample chamber (or the open chamber) would decrease the PTB generation threshold fluence.
3.5 Generation of PT bubbles in homogeneous media and in microsamples
In the next experiment we studied the influence of the above-considered parameters on PTBs in uniformly absorbing micro- and macrosamples: single red blood cells (RBC) and in a solution of hemoglobin (Hb) as in a homogeneous absorber. Thus, we compared the generation of PTBs in micro- and homogeneous samples with the generation of bubbles in transparent media around plasmonic NPs.
Fig. 7. Influence of the height of the sample chamber on the PTB threshold fluence (solid squares) and lifetime (hollow circles) for 30-nm gold NPs, with a single pumping pulse: 0.5 ns, 532 nm.
The influence of the pulse length was similar to that found earlier for gold NPs, although the increase of the PTB threshold fluence for the10-ns pulse was smaller than that in the case of NPs. For the RBC cell it was 8.4 times smaller and for the homogeneous solution of Hb - 2.9 times smaller (Fig. 6). However, we did not detect the influence of the cuvette height and interpulse interval. The most important difference found between the NPs and homogenous absorbing media was described above as the “no-heating” effect for the NP-generated PTBs. In Table 2 we have summarized the differences in PTB generation at nano- and micro-scales.
Table 2. Comparison of the process of generation of PTBs around plasmonic nanoparticles and in homogeneously absorbing media (+ indicates the influence of the specific experimental parameter)
We did not study the influence of the size of the microabsorber on the PTB threshold, because this effect was considered in [36, 67]: the bigger the absorber, the higher is the PTB threshold. However, as we have shown above and in some of our previous works [68, 69] in the case of plasmonic NPs the rule is the opposite: bigger NPs (and clusters) decrease the PTB generation threshold fluence. The bigger NP accumulates much more thermal energy as it is proportional to the NP volume. Next, the increase of the radius of NP stimulates the transition from the bubble nucleus to the expanding bubble by decreasing the surface tension (that is inversely proportional to the radius) and viscosity. Thus the increase of the NP size lowers an optical fluence threshold for a PTB generation.
4. Discussion
4.1 Laser-induced temperature, pressure and size of plasmonically generated bubbles.
The size of the heated volume of the medium during pulsed PT interaction is determined by the size of the heat source and by the thermal diffusion radius Rt = (24aτe)1/2 that depends upon the pump pulse duration. In homogeneous media and for a relatively short laser pulse the size of a heat source is determined by the diameter of the pumping pulse (7000 nm) because Rt is much smaller. Thus, the heated volume of a homogeneous absorber is determined by the laser beam aperture (Table 3). When NPs act as heat sources in transparent media, the volume of a heated medium is determined by that of a NP and by the thermal diffusion radius. Thus, the heated volume of the medium around a NP Vh(NP)≈4/3π[(0,5Dnp+(24aτe)1/2)3 - Dnp 3/8] depends mainly on the pulse duration. The space scale of thermal processes in homogenous media and in microabsorbers are determined by the size of an optical absorber, while for nanoabsorbers the space scale of thermal processes is determined by the duration of a laser pulse. This caused 30 time increase of the heated volume when the pulse length was increased from 0.5 ns to 10 ns and explains the increase of the PTB threshold fluence for the longer pulse.
Laser-induced initial temperature of the NPs may be estimated only indirectly. The irreproducible PTBs may imply melting of NPs, which practically turns off the plasmonic mechanism of energy conversion. This corresponds to the temperature of gold melting (1337 K). Reproducible PTBs that were detected at the fluence levels close to the PTB threshold may imply a minimal temperature level in the range from 370 K to 500 K (for a normal pressure). These numbers estimate the initial laser-induced temperature of the medium around a NP. Heat transfer models for low laser-induced temperatures in the range well below the melting threshold [3, 15, 70, 80] show that heat is transferred within 100–300 ps into the water nanoenvironment with the thermal radii shown in Table 3. A more precise estimation requires reliable data on the actual value (and dynamics) of the optical absorption cross-section of the NP in the high temperature range including NP melting. Most of the models [63, 70, 71] use the absorption cross-section as a constant, which is not true: it was shown by Otter in 1961 that the optical absorbance of gold deteriorates significantly (more than one order of magnitude) as the temperature approaches the melting threshold, and more recent works have demonstrated the temperature dependence of the absorbance cross-section of plasmonic NPs [73–78]. Recently we have shown experimentally that at high laser-induced temperatures the behavior of plasmon resonances and PT efficacy of gold NPs significantly differ from that at a lower temperature [72].
The next temperature effect discovered is the above-reported “no-heating” effect during PTB generation. We have detected laser-induced heating of the bulk medium at subthreshold laser fluencies. However, at higher fluencies (and hence higher initial laser-induced temperatures) and during the PTB generation around NPs, there was no detectible residual bulk heating for all NPs and their clusters studied (Fig. 4(a) and 4(b)). Residual heating of the bulk medium was clearly detected by us when the bubbles were generated in a homogeneous absorbing solution. Thus, the discovered fact is also specific for the PT processes on a nanoscale and calls for further investigation.
We did not observe pressure waves in our 3-ns delayed images (in [20] the shock waves were detected for a 30-ps pump pulse by a similar technique). The pulse length of 0.5 ns is long enough to avoid significant pressure build up in NPs so that no strong pressure waves are to be expected. However, some fronts with compression and rarefaction waves may result from the initial temperature rise. This may explain the experimental dependence of the threshold on cuvette height, as has been reported above. Therefore the optimization of the cuvette geometry may provide an additional decrease in the bubble generation threshold fluence and temperature as was observed previously [98–101] for micro- and macrobubbles.
Although we could not directly measure a maximal diameter of PTBs, it can be estimated by the measuring the bubble life and using the available models of the bubble dynamics [38, 42, 45, 81–84], as well as experimental data on micrometer-sized bubbles whose diameters were directly correlated with their lifetimes [45, 101–103]. Based on these data, we have estimated the diameter of PTB with a minimal lifetime (15–20 ns) to be at about 460 nm (based on the data from [34]). Though we have not found the correlation between the size of a nanoabsorber and a minimal lifetime of a PTB, it is natural to assume that the bubbles generated around small single NPs would be smaller than those generated around much bigger NP clusters. A maximal diameter of the bubbles generated around 35-nm gold NPs in water was reported to be 250 nm [63–66]. In the cited works the laser-induced fragmentation of the gold NPs was also detected, and this explains the poor reproducibility of PTBs in our experiments. Therefore we may hypothesize that a maximal diameter of the PTB was above 200 nm and below 400 nm (for 30-nm gold NPs). It is interesting to note that we have never detected bubbles with the lifetime shorter than 15 ns irrespective of the type of NP and laser pulse fluence. There is also the possibility of measuring the PTB diameter through optical scattering imaging, because the amplitude of the light scattered by PTB correlates with the PTB diameter [34,104,105]. However, this method requires further optimization.
Our results show that the mechanism of PTB generation depends on many factors related to a laser pulse, NP size, NP shape and NP aggregation state, and even on the sample chamber. The foregoing results may help in the development of a realistic model of nano-scale PTBs that should include the following factors: (1) the NP absorbance cross-section as a function of the NP temperature, (2) the laser pulse fluence as a function of the vapor bubble radius around a NP, (3) potential melting and vaporization of the NP surface layer, and (4) heat transfer between the bubble and surrounding medium and under the conditions of bubble generation.
4.2. PTB as optical probes
We employed two optical techniques that use scattering of the probing laser radiation: imaging detects a pulsed signal from the zero level while, the response mode detects a continuous signal as a deviation from the specific base level. These techniques have different properties that are summarized in Table 3. It is important to note that technically both techniques can be used simultaneously and in one experimental setup. As can be seen from our results, such a combination of time-resolved imaging with the monitoring of the PTB response provides the most reliable detection of bubbles.
Table 3. Comparison of the features of two optical scattering methods for sensing PTBs
The optical scattering is a recognized method for sensing vapor and air bubbles of macro-size [34, 104, 105]. The bubbles of submicrometer size can also be sensed by optical scattering, as we have demonstrated above (not to mention prior works [34, 104, 105]). Laser-induced PTBs of small size generated around NPs and their clusters may be used for optical imaging of a specific target with the sensitivity being much higher than that of optical imaging of plasmonic NPs. With its ability to amplify the optical scattering, the PTB can be considered as a new type of the optical sensor that can be selectively activated “on demand” around plasmonic NPs coupled to a specific target. The origin of the bubble can be linked to a specific target molecule through the vector-based delivery of NPs. Thus, the PTB imaging may provide efficient optical detection of a small target even when the latter is surrounded by highly a scattering background. Speaking about biomedical applications of PTBs as image sensors, we would like to point out two factors. First, unlike fluorescent probes the bubbles do not exist until and after they are generated, and, second, gold NPs are much less toxic than any fluorescent probes. Therefore the influence of PTB imaging on physiological processes in cells prior to the bubble generation can be minimal. The threshold mechanism of bubble generation provides the selectivity of an optical signal and thus increases the signal-to-noise ratio of imaging. The time-resolved imaging may help in differential detection of small (noninvasive diagnostics) and large (disruptive therapeutics) bubbles around the same NP. The universal PTB imaging may be realized in microscopy, flow cytometry, endoscopy, and in other optical methods. The bubble imaging methods can be applied for optical guidance of therapeutic processes, where bubbles occur as primary or secondary phenomena (in particular, in laser and ultrasound methods). The nontoxic properties of gold nanoparticles and «on demand» feature of bubbles may provide non-invasive monitoring and screening of living cells in vitro and in vivo.
5. Conclusions
In some PT applications of plasmonic NPs and PTBs, the local mechanical effect is more important while the thermal effect may be unneeded. This is a typical situation for biomedical tasks that involve a living tissue. Thus, the minimization of the threshold laser fluence and of the initial laser-induced temperature may be crucial for successful application of plasmonic NPs. Our results may help in designing optical plasmonic devices, methods and models that employ NP-mediated generation of vapor bubbles on a nano-scale and can be summarized as:
1. The mechanism of the generation of photothermal bubbles around plasmonic nanoparticles differs from the mechanism of bubble generation around micro- and macroabsorbers:
- the bubble generation threshold fluence of laser pulse significantly depends on the particle size and on the optical pulse duration;
- an increase in the size of particles and their clusterization, and also the shortening of the laser pulse provide a significant decrease in the threshold fluence and in the initial laser-induced temperature.
- nanoparticle-generated bubbles may temporally and spatially localize laser-induced thermal field and prevent residual heating of the bulk media.
2. Optimization of the bubble generation conditions may provide the minimal laser pulse fluence and hence the maximal efficacy and selectivity of the plasmonic interactions by means of:
- optimization of the pulse duration in the subnanosecond range;
- use of the pulse sequence (train) with an optimized interval between pulses;
- optimization of the size of nanoparticles and their aggregation state, in particular, the use of nanoparticle clusters instead of single particles;
- increase in the size of the cuvette, if bubbles are generated in closed volumes.
3. The optical scattering properties of photothermal bubbles provide the possibility of their detection with high sensitivity and temporal resolution. Bubbles amplify optical scattering relative to that of plasmonic nanoparticles. This optical property of bubbles together with their “on-demand” nature and small size provide the basis for developing a new type of optical probes.
Acknowledgment
The author thanks Professors J. Hafner, R. Drezek (Rice University), and L.Loterini (University Perugia) for the kindly provided samples of gold nanoparticles and Dr. E. Hleb (A.V. Lykov Institute) for her help with experimental procedures.
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