1. Introduction

Minimally invasive photodynamic therapy (PDT) is a promising cancer treatment that combines the use of photosensitizing (PS) drugs and light in the presence of oxygen to initiate photochemical reactions that culminate in the generation of a highly reactive product termed single oxygen (¹O₂), which can rapidly cause significant toxicity leading to irreversible apoptosis and necrosis of tumor cells [1–3]. This procedure involves local or systemic administration of a PS agent, followed by irradiation with a light at a wavelength corresponding to an excitation band of the PS and delivered to virtually organs in human body by means of flexible fiber-optic devices. Obviously, the light source and light delivery devices play an essential role in PDT. According to most tissue modeling, red light in the 600−730nm spectral region penetrates most deeply through tissue allowing treatment of thicker lesions, which is 50−200% more than light in the 400−500nm region, and has more sufficient energy to initiate a photodynamic reaction to generate ¹O₂ [4,5]. Therefore, high-directivity and high-brightness light source in 600−730nm region is exceedingly desirable for PDT surgery.

Recently, both lasers with perfect directivity and strong intensity and light-emitting diodes (LEDs) with relatively narrow spectral bandwidths and high fluence rates have been specifically designed for PDT treatment [5]. However, light diffusely scattered or mis-located from the target area may accidentally irradiate large areas of the normal tissue due to the huge power density, resulting in inflammation, pain, swelling, burn, and scarring. Although LEDs can be coupled with optical fiber, the low coupling efficiency limits the application of LEDs, and owing to their narrow excited spectral bandwidth, the application of multiple PS to improve the therapy efficiency is also limited. Amplified spontaneous emission (ASE) fluorescence generated in rare-earth (RE) ions doped glass channel waveguide, which has broadened bandwidth and can be adjusted by RE ion concentration and pumping power, provides adequate intensity, good directivity and efficient coupling efficiency, and has the potential to be a promising candidate for light source in PDT treatment. As luminescence center, Sm³⁺ can be used as activators in various glass hosts for efficient emissions in visible and NIR wavelength since its lasering state exhibits higher quantum efficiency and multifarious radiative emission channels [6–24]. It is well known that the emission transitions of Sm³⁺ give favorable red fluorescence, which located in the absorption maximum region of the PS currently used in therapy or clinical trials [25–29]. In minimally invasive PDT surgery, high-directivity light source at 600−730nm wavelength can penetrate deeper into tissue and improve the operative quality. Favorable ASE fluorescence in Sm³⁺-doped glass channel waveguide can satisfy the above requirements and the integrated waveguides will become the candidate light source for minimally invasive PDT treatment.

In this work, high-quality acid-resistant aluminum germanate (NMAG) glasses with lower phonon energy (≤900cm⁻¹) and perfect dispersibility of RE ions are employed in making Sm³⁺-doped ion-exchanged glass channel waveguide. Under the excitation of a 488nm Ar⁺ laser, a clear and compact red ASE trace that can be used as excitation light source for minimally invasive PDT treatment is observed and investigated. 78% photons of ASE fluorescence in visible region are located in 600−730nm wavelength range and the larger emission cross-sections of the emission transitions indicate that the intense red emitting in 600−730nm region can be efficiently achieved in Sm³⁺-doped NMAG glass waveguide under appropriate excitation conditions, such as commercial UV laser diode and Ar⁺ optical laser.

2. Experiments

Sm³⁺-doped NMAG glasses were prepared from high-purity Na₂CO₃, MgO, Al₂O₃, GeO₂, and Sm₂O₃ powders according to the molar composition 23Na₂O-2MgO-22Al₂O₃-(53−x)GeO₂- xSm₂O₃, and x = 0.1 and 1mol% for low- and high-concentration dopings, respectively. The glasses were melted in pure alumina crucibles and the preparation procedure is described in Ref. 30. For optical measurements, the glass samples were sliced into pieces and polished with two parallel sides. The density of the 1mol% Sm₂O₃ doped NMAG glasses was measured to be 3.185g⋅cm⁻³ by Archimedes method, and the number density of Sm³⁺ ions was calculated to be 4.022×10²⁰cm⁻³. Using a Metricon 2010 prism coupler, the refractive indices of the high-concentration doping sample were measured to be 1.5825 and 1.5659 at 632.8 and 1536nm, respectively. The refractive indices of the sample at all other wavelengths can be calculated by Cauchy’s equation $n=A+B/{\lambda }^2$ with A = 1.5625 and B = 8006nm². UV/VIS/NIR absorption spectrum of the glass sample was recorded with a Perkin-Elmer UV/visible/near-IR Lambda 19 double-beam spectrophotometer, and Fourier IR transmittance spectrum was obtained by a Spectrum One-B Fourier transform IR spectrometer. Visible emission spectrum was determined by a Jobin Yvon Fluorolog-3 spectrophotometer equipped with an R928 photomultiplier tube (PMT) detector and a commercial CW Xe-lamp was adopted as the pumping source. Fluorescence decay curves were recorded under the same setup using the R928 PMT detector and a flash Xe-lamp. The luminescence pictures were taken using a Sony SLT-α33 digital camera.

Before preparing the K⁺–Na⁺ ion-exchanged channel waveguide, 1mol% Sm₂O₃ doped NMAG glass substrate was optically polished and cleaned. A 150nm-thick high-quality aluminum film was deposited on the glass surface using an Edwards Auto 306 thermal evaporator, and then 6μm wide channels were opened by standard micro-fabrication process and wet chemical etching method. The ion-exchange process for the channel waveguide was performed in pure KNO₃ molten bath for 2 hours at 390°C. After cooling down to room temperature, the aluminum film was removed and two end-faces of the waveguide were polished for further optical measurement. The surfaces of the ion-exchanged channel waveguide were investigated using an atomic force microscope (AFM). Laser light at 1.55μm wavelength was coupled into the ion-exchanged waveguide, and the near-field mode patterns at the output facets were examined using a video camera. The optical spectrum measurement of the Sm³⁺-doped NMAG glass waveguide was carried out when the output light from the end-facet of the waveguide was collected by a single-mode fiber connected to YOKOGAMA AQ6375 optical spectrum analyzer (OSA). A 488nm Ar⁺ laser (Coherent INNOVA 90) was adopted as the pump source, and the laser light was focused into a single-mode fiber to couple the output light from the fiber into the waveguide.

3. Results and discussion

Sm³⁺-doped acid-resistant NMAG glasses are visually transparent and homogeneous as shown in Fig. 1(a) . A thermal K⁺−Na⁺ ion-exchange process at 390°C for 4h was carried out to fabricate optical slab waveguide in Sm³⁺-doped NMAG glasses. The refractive index as a function of the diffusion depth at 632.8nm was derived and presented in Fig. 1(b), which was obtained from the measured mode indices using an inverse Wentzel−Kramer−Brillouin (IWKB) method [31]. The surface refractive index of the waveguide n₀ was calculated to be 1.5895, and the maximum refractive index change Δn = n₀−n_sub was calculated to be 0.0070. Figure 1(c) and 1(d) depict typical measurement results of the slab waveguide, of which the peaks represent the detected modes of the waveguide. Here, four complete and one incomplete modes were demonstrated at 632.8nm wavelength, and one complete and one incomplete mode at 1536nm, respectively, showing that it is feasible to fabricate a monomode waveguide in the wavelength of 1400−1800nm on NMAG glasses.

 

Fig. 1 (a) Photograph of Sm³⁺-doped NMAG glasses under nature light. (b) Index profile at 632.8nm for slab waveguide by ion-exchanging at 390°C for 4h. (c) Intensity of reflected light versus index value with 632.8nm laser source. (d) Intensity of reflected light versus index value with 1536nm laser source.

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Take the experimental parameters for the slab waveguide as a reference, the condition of K⁺−Na⁺ ion-exchanged process was selected to be 2 hours at 390°C in order to achieve a favorable single-mode Sm³⁺-doped NMAG glass channel waveguide. The AFM image of the channel surface section is presented in Fig. 2(a) , showing the dent caused by the thermal ion-exchange process. The picture confirms that a K⁺−Na⁺ ion-exchanged channel waveguide has been fabricated in Sm³⁺-doped NMAG glasses. The near-field mode patterns at the output facets were examined using a video camera when 1.55μm laser was coupled into the ion-exchanged glass waveguide. As shown in Fig. 2(b) and 2(c), the mode profile of the waveguide channel indicates that the waveguide is single mode at 1.55μm, and the mode field diameter was measured to be 9.6μm in the horizontal direction and 6.0μm in the vertical direction, respectively, which indicates an excellent overlap with that of a standard single-mode fiber [32].

 

Fig. 2 (a) AFM image of the channel section. (b) Near-field mode pattern of Sm³⁺-doped NMAG glass channel waveguide at 1550nm. (c) A 3D representation of the near-field mode pattern of the channel waveguide at 1550nm. (d) ASE fluorescence generation and transmission in Sm³⁺-doped NMAG glass channel waveguide under the excitation of 488nm wavelength laser pumping.

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Sm³⁺-doped NMAG glass channel waveguide exhibits a bright and compact ASE fluorescence trace with strong directivity under the excitation of 488nm laser, as shown in Fig. 2(d). With increasing the pumping power, the fluorescence intensity is increased and the spectral width becomes narrow. The intense ASE fluorescence observed in the waveguide can be perfectly coupled into the fiber, and the collective fluorescence from the output end of the fiber has potential applications for diagnosis and localization of cancer in PDT. In order to understand the fluorescence characteristic deeply, spectral power distribution of the ASE fluorescence in Sm³⁺-doped NMAG glass waveguide was recorded by collecting the output light from the end-facet of the waveguide via a single-mode fiber connected to the OSA in the case of low laser pumping. In the OSA spectrum, four main ASE emission bands of Sm³⁺-doped NMAG glass waveguide are observed at 565.5, 601.0, 649.0, and 709.5nm as shown in Fig. 3(a) , respectively. The photon distribution of the ASE fluorescence in the waveguide was calculated and illustrated in Fig. 3(b) based on the spectral power distribution. The integrated photon ratio of four bands was calculated to be 7.2%: 44.1%: 38.6%: 10.1%, respectively, and 78% photons in the visible region of ASE fluorescence are located in 600−730nm wavelength range, indicating that the ASE fluorescence in this region is efficient. Further operations by increasing the coupling laser pumping and raising the coupling efficiency are benefit to achieving the desirable intense red ASE fluorescence, which matches the absorption peaks of most PS so that can provide enough energy to excite oxygen to its singlet state (¹O₂) and rapidly cause significant toxicity leading to cancer cell death via apoptosis or necrosis in the PDT treatment.

 

Fig. 3 (a) OSA spectrum recorded from the output end facet of K⁺–Na⁺ ion-exchanged Sm³⁺-doped NMAG glass channel waveguide under the excitation of 488nm wavelength laser pumping. (b) Photon distribution of Sm³⁺-doped NMAG glasses under 488nm excitation. (c) Visible emission spectrum of 1mol% Sm₂O₃ doped NMAG glasses under 488nm excitation. (d) Excitation spectrum for 598.5nm emission in Sm³⁺-doped NMAG glasses.

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Figure 4 shows a schematic diagram of Sm³⁺-doped NMAG glass channel waveguide used as PDT irradiation light source for cancer treatment in mini-invasive surgery. The pumping laser as the pump source, which can chosen to be commercial laser diode or Ar⁺ optical laser, is connected to the input end of Sm³⁺-doped NMAG glass channel waveguide. An optical fiber is adopted to conduct the output signal of the NMAG glass waveguide into the mini-invasive PDT surgery device, and the channel waveguide aperture can be adjusted through ion-exchanging time to match different types of optical fibers, which is helpful to obtain more efficient coupling efficiency. By adjusting the concentration of Sm³⁺ and the waveguide aperture, the output light power can be expected up to 100mW, which is suitable for most approved PS, and the spectral width of the light source is derived to be 15−20nm, which will be decreased to 5−10nm by increasing the pumping power. The ASE fluorescence also can be coupled into fibers with diffusing tips to treat tumors in the urinary bladder and the digestive tract. By the use of modern fiber-optic systems and various types of endoscopy, the ASE fluorescence can be targeted accurately to almost any part of human body.

 

Fig. 4 Schematic diagram of Sm³⁺-doped NMAG glass channel waveguide used as PDT irradiation light source for cancer treatment in mini-invasive surgery. Inset: Fluorescence from 1mol% Sm₂O₃ doped NMAG glasses under 365nm excitation.

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In order to further understand the potential performance of Sm³⁺-doped NMAG glass channel waveguide in PDT treatment, the radiative transition characteristics of Sm³⁺ ions in NMAG glass substrate are essential to be exposed in reflecting the efficiency of ASE fluorescence. Here, Sm³⁺-doped NMAG glasses exhibit bright orangish-red fluorescence under the excitation of 365nm UV light, as shown in the inserted photo of Fig. 4. The visible emission spectrum of Sm³⁺-doped NMAG glasses under 488nm excitation is presented in Fig. 3(c), and four dominant fluorescence bands peaked at 562.0, 598.5, 645.5, and 705.0nm are attributed to f−f transitions: ⁴G_5/2→⁶H_5/2 ⁴G_5/2→⁶H_7/2, ⁴G_5/2→⁶H_9/2, and ⁴G_5/2→⁶H_11/2. Figure 3(d) shows the excitation spectrum monitoring at 598.5nm, and the efficient excited wavelength range of Sm³⁺ in NMAG glasses covers the whole long-wavelength UV, blue and bluish-green spectral ranges well, indicating that commercial UV and blue laser diodes, blue and bluish-green LEDs and Ar⁺ optical laser are powerful pumping sources for Sm³⁺-doped NMAG glasses.

The absorption spectrum of Sm³⁺-doped NMAG glasses from 300 to 2200nm shows thirteen absorption bands peaking at 343.0, 359.5, 373.5, 401.5, 473.5, 939.0, 1071.0, 1218.0, 1361.5, 1463.5, 1521.0, 1582.5, and 1955.0nm, which associate to the absorption transitions from the ⁶H_5/2 ground state to the excited states, as labeled in Fig. 5(a) . The radiative transitions within the 4f⁵ configuration of Sm³⁺ can be analyzed by the Judd-Ofelt theory based on the absorption spectrum [33–35]. Judd-Ofelt intensity parameters Ω_t (t = 2, 4, 6) are derived to be 4.662×10⁻²⁰, 4.645×10⁻²⁰, and 1.979×10⁻²⁰cm² by a least-squares fitting approach, respectively. The root-mean-square deviation was 3.3×10⁻⁷, indicating that the calculation process was reliable. The intensity parameter Ω₂ has been identified to be associated with the asymmetry and the covalency of the lanthanide sites, and Ω₄ and Ω₆ are related to the bulk property and rigidity of the samples, respectively. In the NAMG glass system, Ω₂ is larger than the values of 1.46×10⁻²⁰, 1.94×10⁻²⁰, and 3.03×10⁻²⁰cm² in phosphate [36], silicate [37], and zinc−bismuth−borate glasses [38], respectively, showing a strong asymmetrical and covalent environment around Sm³⁺ ions. The ratio of Ω₄/Ω₆ in NMAG glasses is 2.347, which indicates a higher optical quality. Using the Ω_t values, some important radiative properties including spontaneous transition probabilities (A_ed and A_md), branching ratios (β), and radiative lifetime (τ_rad) for the optical transitions of Sm³⁺ in NMAG glasses were calculated and listed in Table 1 The predicated spontaneous emission probability A_rad for the transitions ⁴G_5/2→⁶H_J (J=5/2, 7/2, 9/2, and 11/2) are derived to be 25.85, 131.03, 140.85, and 35.34s⁻¹, respectively, which are higher than those in silicate [37] and fluorophosphates glasses [39]. The energy level diagram and the predicted emissions are schematically illustrated in Fig. 5(b).

 

Fig. 5 (a) Absorption spectrum of 1mol% Sm₂O₃ doped NMAG glasses. Inset of (a): IR transmittance spectrum of Sm³⁺-doped NMAG glasses (sample thickness is 3.40mm). (b) Energy level diagram of Sm³⁺ ion in NMAG glasses.

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Table 1. Predicted emission probabilities, branching ratios, and radiative lifetime of Sm³⁺ in NMAG glasses

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The Fourier IR transmittance spectrum of Sm³⁺-doped NMAG glasses is shown in the inset of Fig. 5(a). The IR transmission sideband (R, wave number at 10% transmittance) reflects the maximum phonon energy (E) of the glass sample in some extent. The maximum phonon energy in Sm³⁺-doped NMAG glasses was estimated to be 838cm⁻¹ by the empirical formula E=92.9+0.4257R, where R was identified to be 1750cm⁻¹ in present case. Compared with the maximum phonon energy in borate (1400cm⁻¹), phosphate (~1200cm⁻¹), silicate (~1100cm⁻¹), and tellurite (~750cm⁻¹) glasses [40], the value in NMAG glasses is lower than those of most oxide glasses, which is beneficial in achieving efficient multi-channel transition emissions of Sm³⁺.

Figure 6(a) shows the measured decay curves of the ⁴G_5/2 level for 0.1 and 1mol% Sm₂O₃ doped NMAG glasses. The decay curve is approximately single exponential for low-concentration doping, and non-exponential for high-concentration case due to donor (excited state ion)−acceptor (ground ion) energy transfer (ET) through cross-relaxation (CR). The experimental lifetimes of the fluorescent ⁴G_5/2 level have been determined to be 2.234 and 0.628ms for 0.1 and 1mol% Sm³⁺-doped NMAG glasses by finding the average lifetime [41], and the quantum efficiencies (${\eta }_{\text{q}}={\tau }_{\text{exp}}/{\tau }_{\text{rad}}$) for ⁴G_5/2 level in 0.1 and 1mol% Sm₂O₃ doped NMAG glasses are calculated to be 85% and 24%, respectively. The measured lifetime (τ_exp) can be expressed as $1/{\tau }_{\text{exp}}=1/{\tau }_{\text{rad}}+W_{\text{MPR}}+W_{\text{ET}},$ where W_MPR is the multiphonon relaxation (MPR) rate, and W_ET is the rate of energy transfer. According to the Miyakawa–Dexter theory, the W_MPR can be expressed by the formula $W_{\text{MPR}}=W_0\exp \left(-\alpha \Delta E/\hslash \omega \right),$ where α, ΔE, W₀ and $\hslash \omega$ are the positive host-dependent constant, energy gap to the next lower level, decay rate when ΔE=0 and phonon energy of the host, respectively. As there is a large energy gap of around 7000cm⁻¹ between the ⁴G_5/2 level and the next lower level and it requires at least 8 intrinsic phonons to bridge the interval in the nonradiative relaxation process, the multiphonon relaxation rate W_MPR can be negligible and the W_ET is given by $W_{\text{ET}}=1/{\tau }_{\text{exp}}-1/{\tau }_{\text{rad}}$ [42–44]. The W_ET for the ⁴G_5/2 level of low- and high-concentration doping are calculated to be 69 and 1214s⁻¹, respectively. Although the quantum efficiency for ⁴G_5/2 level of Sm³⁺ in 1mol% Sm₂O₃ doped NMAG glasses is decreased compared with 0.1mol% Sm₂O₃ doped NMAG glasses due to the energy transfer, the high-concentration doping of Sm³⁺ ion in NMAG glasses for ion-exchanged channel waveguide is necessary for the integrated compact channel waveguide structure to achieve efficient ASE fluorescence.

 

Fig. 6 (a) Fluorescence decay curves of the ⁴G_5/2 level for 0.1mol% (curve 1) and 1mol% (curve 2) Sm₂O₃ doped NMAG glasses. (b) Simulated emission cross-section profiles for the emission bands of Sm³⁺ in visible wavelength region.

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The stimulated emission cross-section σ_em is an important parameter to evaluate the energy extraction efficiency for optical material. From the experimental luminescence spectrum, the σ_em for the transition emissions arising from ⁴G_5/2 level of Sm³⁺ can be evaluated via the Fuchtbauer–Ladenburg (FL) formula:

4. Conclusion

Sm³⁺-doped ion-exchanged aluminum germanate (NMAG) glass channel waveguide was prepared and a dynamic red amplified spontaneous emission (ASE) trace is observed under the excitation of a 488nm Ar⁺ laser. 78% photons of ASE fluorescence in visible region located in 600−730nm wavelength range was obtained and the large emission cross-sections of the emission transitions indicate that the intense red emitting in 600−730nm region can be efficiently achieved in Sm³⁺-doped NMAG glass waveguide. Based on the efficient ASE fluorescence, a schematic diagram of Sm³⁺-doped NMAG glass channel waveguide used as PDT irradiation light source for cancer treatment in mini-invasive surgery was proposed. High-directivity and high-quality ASE fluorescence, which matches the absorption band of most photosensitizers (PS) currently used in therapy or clinical trials, can be efficiently achieved in high-concentration Sm³⁺-doped NMAG glass channel waveguides, and the favorable light is a promising light source applied for in minimally invasive photodynamic therapy (PDT) surgery.