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We developed a novel dopamine sensing and measurement technique based on aggregation of gold nanoparticles in random lasers. Dopamine combined with copper ions triggers the aggregation of gold nanoparticles and thus affects the performance of random lasers. Dopamine sensing can be achieved using four parameters which are sensitive to the presence of dopamine, that is emission peak shift, emission linewidth, signal-to-noise ratio (peak emission intensity / noise) and random lasing threshold. The dopamine is most sensitively detected by a change in the emission linewidth with a limit of detection of 1 × 10−7 M, as well as by an increase in the lasing threshold. The dopamine concentration from 1 × 10−7 M to 1 × 10−2 M can be determined by calibrating with the laser threshold.
© 2015 Optical Society of America
1. Introduction
Dopamine is a catecholamine neurotransmitter distributed in the brain tissues and body fluids of mammals [1]. It has important roles in the function of the central nervous, renal and cardiovascular systems. In particular, it is important in Parkinson and Huntington’s diseases which affect the human brain and are accompanied by a change in dopamine concentration. A deficiency of dopamine in the brain leads to ‘out of control’ muscle activity in Parkinson’s disease, while excessive dopamine leads to Huntington’s disease [1–3]. Therefore, the measurement of dopamine is significant in diagnosis, monitoring, prevention and treatment of these conditions.
Several authors have used optical methods to sense dopamine, including techniques based on nanoparticle aggregation, and colorimetric assays. In particular, Su et al. [2] used copper ions to enhance the aggregation of gold nanoparticles by dopamine. The limit of detection was 2 × 10−7 M, determined by a colour change and absorption peak shift. Chen et al. [4] used melamine-induced aggregation of gold nanoparticles to detect dopamine in a complex medium of human urine, where they achieved a limit of detection of 33 nM. The lowest detection limit of dopamine reported in the literature is 0.3 nM [3]. The detection mechanism in this work was based on through fluorescence resonant energy transfer (FRET) from the silicon nanoparticles to dopamine.
This study demonstrates the first time application of random lasers with incoherent feedback to detect dopamine based on dopamine-induced aggregation of gold nanoparticles. Random lasers have been reviewed in ref [5]. In these optical systems, light undergoes multiple scattering events in the random medium while it is simultaneously amplified by stimulated emission in the gain medium. The random and gain media are mixed together. The lasing threshold is reached when the total gain exceeds the total losses. Features of random lasing including the presence of laser emission, lasing threshold, polarization and coherence of emission are determined by properties such as surface roughness of the scatterers [6, 7] and they may also depend on plasmonic effects [8, 9]. The use of specific nanoparticle shapes [10, 11] and bio-inspired materials [12] have also been considered in earlier studies of random lasers. While nanoparticle aggregation is widely exploited in biosensing, to the best of our knowledge, it has not been used to detect trace quantities of biomolecules in random lasers. We hypothesised that since multiple light scattering and gain are important elements in random lasers, in order to provide feedback and light amplification, the presence of analyte affecting aggregation may be detected via random lasing. This is because the aggregation of nanoparticles may lead to sedimentation and it also reduces the number density of scatterers. When multiple light scattering is reduced due to reduced particle density, the feedback is also reduced which thus affects the random laser performance. The effect of aggregated silver nanoparticles in Rhodamine 6G dye lasers was studied by Noginov et. al [13]. They observed an increased lasing threshold and reduced laser slope efficiency.
Dopamine detection using lasers could be a novel alternative to current techniques which involve chemical or biological effects, provided there is sufficient detection sensitivity. To explore this, we investigated different sensing parameters such as emission peak shift, emission linewidth, signal-to-noise ratio and lasing threshold. We found that the aggregation results in an emission peak red-shift of ~1 nm and broadening of the emission linewidth. We also observed a decrease of the signal-to-noise ratio (SNR) and an increase of the lasing threshold with aggregation. We were able to measure dopamine concentration in a wide dynamic range based on the random lasing threshold. The limit of detection for dopamine in our system was found to be 1 × 10−7 M.
2. Sample preparation and characterisation
Various concentrations of dopamine in water (1 × 10−8 - 1 × 10−2 M) (Sigma Aldrich) were added to gold nanoparticles (particle density, ρ ~1.8 × 1011 cm−3, size ~20 nm) (Ted Pella) and stirred for 5 minutes before 0.15 mM copper (II) chloride (Sigma Aldrich) was added. The final solution was 0.35:0.65 methanol:water. The solution was stored at room temperature for 30 minutes for aggregation before recording the UV-vis spectra [2]. The absorption / extinction of Rh640 / gold nanoparticles was measured by a Cary Spectrometer (Varian) while the fluorescence was measured by a Fluorolog Spectrofluorimeter (Horiba Jobin Yvon). Rhodamine 640 (Exciton, 1 × 10−4 M) was added as the random laser gain medium.
The scattering mean free path, ls, ls = 1 / (ρσs), for the gold nanoparticles with 0 M of dopamine is ~139 cm, where ρ and σs refer to the particle density and scattering cross section respectively. σs is 4 × 10−14 cm2 at the optical wavelength of λ ~532 nm [8, 14, 15]. As ls >> L (sample size ~3 mm), the random laser with gold nanoparticles and no dopamine is in the weakly scattering regime [8]. With added dopamine, the ls increases due to reduced particle density.
We observed the aggregation of gold nanoparticles due to addition of dopamine and copper (II) chloride using transmission electron microscopy (TEM) (Fig. 1). A small amount of sample was dropped on a grid and dried in vacuum. It was imaged through a transmission electron microscope (Philips CM10 transmission electron miscroscope, 100 kV with Olympus SIS Megaview G2 Digital Camera, resolution ~1376 × 1032 pixels). The size of the gold nanoparticles increases and the shape becomes irregular after aggregation as shown in the TEM images in Fig. 1.
Fig. 1 TEM of gold nanoparticles with 0.15 mM copper (II) chloride and (a) 0 M, (b) 1 × 10−7 M, (c) 1 × 10−5 M and (d) 1 × 10−3 M of dopamine concentration. The scale bar end to end is 500 nm.
3. Optical pumping experiments
The samples were excited with a Q-switched, frequency-doubled Nd:YAG laser (532 nm, 10 Hz, 4 ns) with a 3 mm pump diameter at an angle of 45° to the normal to the front face of a quartz cuvette (1 cm × 1 cm) and the emission light was collected from the front face of the cuvette at 30° to the normal by a lens (f = 5 cm) and measured by a fibre-coupled spectrometer (Ocean Optics, ~1 nm resolution). A thin teflon sheet placed inside the cuvette prevented back-reflection from the cuvette’s faces and a 532 nm edge filter was used to block residual pump light from the spectrometer.
4. Results and discussion
Figure 2 presents the extinction spectra for gold nanoparticle solutions for varying concentrations of added dopamine. This figure shows that the dopamine red-shifts the extinction peak of the gold nanoparticles and the shoulder starts to appear at 650 nm at a dopamine concentration of 1 × 10−7 M. The extinction spectra of the gold nanoparticles change their shape when the gold nanoparticles aggregate [2]. The extinction spectra (Fig. 2) show that the extinction peak at ~530 nm decreases and shifts to the longer wavelength, which is indicative of aggregation. With more dopamine, increased aggregation of gold nanoparticles leads to increased shift in the spectrum. The red-shifted extinction peak was also observed by Su et al. [2].
Fig. 2 Extinction spectra of gold nanoparticles solutions (1.8 × 1011 cm−3, ~20 nm) with varied dopamine concentration (A-I) and 0.15 mM of copper (II) chloride without Rh640. From A to I, the concentrations of dopamine are 0, 0.01, 0.1, 1, 10, 100, 500, 1000 and 6000 × 10−6 M. The green line indicates the excitation at 532 nm.
Figure 3(a)-3(c) show the emission spectra of Rh640 / gold nanoparticles with various concentrations of dopamine and a fixed concentration of Copper (II) Chloride (0.15 mM). A narrow emission peak appears when the lasing threshold is reached. This is apparent as the peak emission intensity increases nonlinearly with the pump energy density [11, 12]. In Fig. 3(c), broad emission spectra are observed for all pump levels and no random lasing occurs. The peak emission intensity and the lasing threshold decrease when the concentration of dopamine is increased (Fig. 3(d)).
Fig. 3 Emission spectra of Rh640 / gold random lasers with copper (II) chloride (0.15 mM) and varied concentrations of dopamine (a) 1 × 10−7 M, (b) 1 × 10−5 M and (c) 1 × 10−2 M for different pump energy densities. The emission spectrum narrows (4 nm) when the lasing threshold is achieved. Figure 3(d) Peak emission intensity of Rh640 / gold random lasers with copper (II) chloride (0.15 mM) and various concentrations of dopamine versus pump energy density.
Dopamine triggers aggregation of gold nanoparticles because dopamine molecules are adsorbed onto the surface of the gold nanoparticles by electrostatic adhesion. Addition of copper (II) chloride assists the aggregation of gold nanoparticles by dopamine through interactions between Cu2+ ions with the amino and hydroxyl groups of the dopamine molecules. Figure 2 shows the spectral absorption of gold with dopamine shifts with the addition of copper (II) chloride. The Cu2+ ions serve as a selective “discriminator and linker” at high gold nanoparticle concentrations, changing the colour of their solutions from wine red to blue [2] due to aggregation.
The first signature of dopamine is a small emission peak wavelength shift, plotted in Fig. 4(a). The small change in emission intensity of the Rh640 / gold / copper (II) chloride random lasers occurs as the size and shape of the gold nanoparticles change due to aggregation, resulting in changes to the localized surface plasmons and energy transfer process [8, 9]. Thus, the emission peak red-shifts (< 1nm) with increased concentration of dopamine above the limit of detection of 1 × 10−7 M.
Fig. 4 Dopamine sensing parameters using random lasers (a) The emission peak wavelength of Rh640 / gold / copper (II) chloride random lasers for various concentrations of dopamine, excited with 85 mJ/cm2. The emission peak wavelength red-shifts for above 10−7 M of dopamine concentration, (b) The emission linewidth of Rh640 / gold / copper (II) chloride random lasers for various concentrations of dopamine at 90% of peak emission intensity, excited with 31 mJ/cm2, (c) Signal to noise ratio (peak emission intensity/noise) of Rh640 / gold / copper (II) chloride random lasers with various concentration of dopamine excited with 85 mJ/cm2 and (d) Comparison of lasing threshold of Rh640 / gold random lasers for various concentrations of dopamine with and without copper (II) chloride. The brown line shows the concentration of dopamine (~1 × 10−7 M to 1 × 10−2 M) measured by the lasing threshold.
The second indicator of dopamine detection by random lasing is determined through the emission linewidth changes of Rh640 / gold / copper (II) chloride for various concentrations of dopamine estimated at 90% of peak emission intensity, as shown in Fig. 4(b). This analysis was done at a low pump energy, 31 mJ/cm2 where Rh640 / gold / copper (II) chloride random lasers with ≥ 1 × 10−7 M of dopamine showed broad spectra and no lasing. The linewidth increased when the concentration of dopamine was increased from 8 × 10−8 to 1 × 10−7 M.
Furthermore, we observed that the random lasing signal-to-noise ratio (peak emission intensity / noise) is also a signature of dopamine (Fig. 4(c)). The signal-to-noise ratio drops from 270 (8 × 10−8 M of dopamine) to 250 (1 × 10−7 M of dopamine), indicating the limit of dopamine detection to be 1 × 10−7 M.
The final parameter which can be exploited for dopamine detection by random lasing is the lasing threshold (Fig. 4(d)). The lasing threshold increases as the gold nanoparticles aggregate, which leads to reduced particle density and increased particle size. Larger gold nanoparticles precipitate and the reduced number density of nanoparticles affects the threshold. The dopamine limit of detection (in the range from 8 × 10−8 to 1 × 10−7 M) was determined from the increased lasing threshold from 31 to 35 mJ/cm2. As the gold nanoparticle / copper (II) chloride solution without dopamine lases in the weakly scattering regime [8], the aggregation of gold nanoparticles significantly increases the scattering mean free path leading to inadequate feedback with higher lasing threshold. The decrease of the localized surface plasmon (LSP) peak at the excitation wavelength as shown in Fig. 2 may also contribute to the reduced emission intensity and increased lasing threshold [8]. The higher lasing threshold of Rh640 / gold / dopamine random lasers with copper (II) chloride (Fig. 4(d)) confirms that copper ions enhance the aggregation of gold nanoparticles by dopamine, increasing the sensitivity of this detection. Figure 4(d) also allows the characterization of the concentration of dopamine from a concentration of 1 × 10−7 M to 1 × 10−2 M using the observed trend with the laser threshold. A large dynamic range of dopamine concentration (~1 × 10−7 M to 1 × 10−2 M) may be measured by calibrating against the lasing threshold as indicated by the brown line in Fig. 4(d).
These results taken together indicate that the limit of dopamine detection using random lasing is ~1 × 10−7 M, as determined through several sensing parameters such as emission peak shift, linewidth, emission peak / noise (signal-to-noise ratio) and lasing threshold .
7. Summary
We demonstrated a useful application for random lasers with incoherent feedback in which the lasers can be used to measure very low dopamine concentration through aggregation of gold nanoparticles, enhanced by copper ions. The detection indicators are the emission peak shift, emission peak linewidth, signal-to-noise ratio and lasing threshold with a dopamine detection limit of ~1 × 10−7 M. The best parameter for dopamine sensing using this random laser scheme is the change in emission peak linewidth. The dopamine concentration can be measured from the lasing threshold over a large dynamic range from 1 × 10−7 M to 1 × 10−2 M. Though this system is not quite as sensitive as alternative chemical schemes of dopamine detection [3, 4], it has promise as a useful application of random lasers in the biomedical field. Studies incorporating dopamine in buffer solutions to imitate normal physiological body conditions are needed for this technique to gain clinical application.
Acknowledgment
We acknowledge funding and support from the ARC Centre of Excellence Program, Centre for Ultrahigh bandwidth Devices for Optical Systems (CUDOS), ARC Centre of Excellence for Nanoscale Biophotonics (CNBP) (grant no: CE140100003), an Australia Endeavour Award for the first author, Microscopy Unit and Macquarie University.
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