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Abstract
Lasing-based sensors have several advantages over fluorescent devices, specifically related to the high light intensity and narrow mode linewidth that can improve the speed and accuracy of the sensor performance. In this work, a microcapillary-based lasing sensor is demonstrated, in which the lasing wavelengths are sensitive to the surface binding of specific materials. In order to achieve this, we utilized lasing into the “star” and “triangle” modes of a conventional microcapillary and tracked the mode positions after the deposition of a polyelectrolyte tri-layer and the subsequent amide binding of carboxy-functionalized polystyrene microspheres. While the lasing mode spectrum becomes increasingly complicated by the addition of the surface layers, careful mode selection can be used to monitor the layer-by-layer surface binding in a mechanically and optically robust device. For polystyrene microspheres, the detection limits were 9.75 nM based upon the lasing mode shift, which compares favorably with fluorescence-based devices. The methods presented in this work could readily be extended to other surface binding schemes and lasing wavelengths, showing that capillary microlasers could be used for many potential applications that capitalize on stable lasing-based detection methods.
© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
1. Introduction
Whispering-gallery-mode (WGM) resonators such as microrings [1–4], toroids [5–7], capillaries [8–11], and spheres [12–15] have been widely investigated for various sensing applications. WGM-based biosensing generally relies on one of two main approaches for measuring the mode structure. The first approach requires an external light source evanescently coupled into the cavity in order to track the resonance changes that occur when a particle (e.g., a virus, protein, or a representative nanoparticle) binds to the sensor surface. Evanescent coupling methods using phase-matched tapered fibers [16], waveguides [17], or prisms [18] are especially common. In these measurements, the cavity resonances are probed by a tunable laser and the modes appear as “dips” in the transmission spectrum. These methods are capable of measuring Q-factors of 109 or higher [19], and can permit single-particle detection via modulation of the Q-factor [20] or by mode splitting [21]. However, certain drawbacks have so far prevented the development of viable applications. These are mainly associated with expense (i.e., for a narrow-bandwidth tunable laser), device fragility, and difficult experimental setup and packaging. Recent work is aimed toward addressing some of these issues [22].
The second approach employs fluorescence spectroscopy to sample the WGMs. These unlabeled sensing schemes rely on the incorporation of the fluorescent material such as quantum dots [23,24] or other chromophores [25] into the cavity architecture. The fluorescence is pumped via free-space excitation with a continuous-wave laser or light-emitting diode and the cavity resonances appear as modulations in the fluorescence spectrum. Measurement of WGMs via fluorescence obviates the need for expensive equipment such as narrow-bandwidth tunable lasers and does not require delicate or sensitive apparatus for coupling into the cavity modes. However, the light levels are extremely low in comparison to tunable laser setups and the emission must be further dispersed in a spectrometer. The Q-factors also tend to be low, due to the inherently wide bandwidth of fluorophores at room temperature [26,27]. Also, many fluorophores are susceptible to photobleaching, although this problem can be minimized by cross referencing schemes [28].
A WGM-based laser has several advantages for sensing applications, including a higher Q-factor and more intense emission spectra as compared to fluorescence-based devices [29]. Microspherical lasers have been demonstrated for biosensing [30,31] and, more recently, nonspecific lasing microcapillaries have been reported [32]. These devices use laser-dye-containing layers as the gain medium. While a significant intensity enhancement and mode narrowing was observed, lasing instabilities seemed to preclude the development of biosensing applications [25]. In related work, thin-walled capillaries containing a laser dye solution in the channel have also been demonstrated for laser-based sensing applications [33].
Stable microcapillary lasing can be induced relatively easily in conventional thick-walled microcapillaries if the channel is filled with a gain medium [34]. The lasing modes are not the WGMs but are instead associated with reflections at both the inner and outer interfaces. These “geometric resonances” were recently demonstrated for non-specific refractive index sensing with sensitivities as high as 1000 nm/RIU [35]. The geometric modes allow the use of robust, thick-walled capillaries rather than the fragile capillaries commonly used for WGM-based sensing [36]. Capillaries have the additional advantage of being inherently fluidic and thus do not require external chambers or fluid handling systems. Thus, the object of this work is to demonstrate and evaluate the first example of specific surface sensing from the geometric modes of a microcapillary device.
2. Experimental methods
The devices were made from fused-silica microcapillaries (n ≈ 1.458 at 600 nm [37]). Glass capillaries with 125-µm inner radius and 160-µm outer-radius were cut into ∼5 cm lengths and the polyimide jacket was removed by ashing in a furnace at 923 K in flowing oxygen. Each capillary was connected to polytetrafluoroethylene tubing with Norland optical adhesive and affixed above a 20x objective lens. The scattered emission was measured from a direction perpendicular to the capillary axis.
The cavity geometric modes were excited using a Photon Technologies Inc. GL-302 dye laser operated at a wavelength of 500 nm, which was pumped by a GL-3300 N2 laser. This setup produced pulses of approximately 1 ns with energies of ∼200 µJ. A repetition rate of 3 Hz was used. The emission was collected with a 20x objective lens, sent through a 550 nm longpass filter, and it was then analyzed using an imaging spectrometer (30 seconds per exposure) (see Fig. 1) with the entrance slit perpendicular to the capillary axis. The fairly long collection times are required by the low repetition rate and resulting low average power (∼0.6 mW) of our laser.
Fig. 1. Diagram of the experimental setup. A representative star mode is illustrated in the capillary glass wall. The call-out on the right side illustrates the PE trilayer and a PS microsphere bound to the final PAH layer.
The capillary channel was then functionalized by using a polyelectrolyte layering method followed by the binding of carboxy-functionalized polystyrene (PS) microspheres:
- 2. A solution of 1 mM rhodamine B (rhB) in water was then pumped into the capillary to establish the lasing baseline measurement (see Sec. 4). Note that lasing experiments are performed while the gain medium (the rhB-water solution) is being pumped through the channel. This was followed by a water rinse before moving to Step 3.
- 3. Next, a solution of 2 mg/mL polyallylamine hydrochloride (PAH) dissolved in a 2.5 M NaCl aqueous solution was pumped at a rate of 0.02 mL/min for 5 minutes followed by a water rinse. PAH has positively charged functional groups [40] that, therefore, should bind electrostatically to the clean capillary surface.
- 4. A solution of 2 mg/mL polystyrene sulfonate (PSS) in 2.5 M NaCl solution was pumped into the capillary at 0.02 mL/min for 5 minutes. The PSS has a negative surface charge and binds electrostatically to the PAH [23].
- 5. Repeat step 3.
- 6. A solution of 1 mM rhB in water was pumped into the capillary and the lasing mode wavelength was then measured in order to observe the mode shifts after the trilayer formation. This was followed by a water rinse before moving to Step 7.
- 7. A solution of 50-nm-diameter PS microspheres (Polysciences; concentrations ranging from 0.05 mg/mL to 2 mg/mL), n-hydroxysuccinimide (NHS; 250 mM), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC; 250 mM) was then injected into the capillary for 30 minutes, followed by a water rinse.
- 8. Finally, step 6 was repeated (rhB solution) in order to determine the lasing mode shifts after PS microsphere binding.
3. Basic theory and simulation
The star and triangle modes arise from reflections and refractions that occur at the inner and outer boundaries of the capillary (Fig. 2(a)). A geometric description of these resonances was recently developed [35]; here, we further these ideas toward a multilayered structure (specifically, a capillary with a single effective channel coating). This coating approximates the PE trilayer described in the previous section, since each individual PE layer is extremely thin compared to the wavelength. The free spectral range (FSR) of the basic star and triangle modes can be written as [35]
Fig. 2. Diagram illustrating star mode and triangle modes in a layered capillary coating PE layer. (a) An example star mode (orange; N = 5) and a triangle mode superimposed in green. (b) Ray paths illustrating Type 1 (red) and Type 2 (green) triangle modes.
For typical capillary sizes (e.g., the 160 µm outer and 125 µm inner diameters used in the experiment to follow and a 60 nm thick the PE multilayer), the FSR of the star and triangle modes is 0.228 and 4.86 THz, respectively (or 0.27 and 5.8 nm at a wavelength of ∼600 nm). The resonant wavelengths are given by:
Adding an effective layer (i.e., a single layer meant to approximate the channel coatings) to the channel wall increases the number of reflections and possible paths for the triangle modes. Since there is now one more boundary, there are at least two “sub-modes” that can form: Type 1, in which the path difference is given by ΔOPL1 = 2(DE – DF) and Type 2 which has a path difference ΔOPL 2 = 2(AB – AC) (Fig. 2(b)). These path differences shift in an opposite sense as the film thickness, t, increases. Thus, a careful selection of the specific lasing modes permits an observation of either a redshift or a blueshift upon the binding of a surface layer.
Considering the ray paths contributing to the Type 2 triangle modes, the path difference can be written as
For the star modes, the film increases the round-trip path length, leading to a redshift. The magnitude of the redshift is expected to be small, since the mode order corresponding to a similar wavelength would be much larger than for a triangle mode. The optical path increase ΔOPLstar in a layered capillary is
The ray picture derived above gives the basic character of the geometric modes of a layered cylindrical structure. In order to visualize the mode field, the device was modeled with 2D finite-difference-time-domain (FDTD) simulations using Lumerical FDTD Solutions. The cell length was 100 nm and perfectly-matched boundaries were used. In order to match the experiment, the structure had to be much larger than the simulation cell size, so each simulation required approximately 1 week on a 2.6 GHz computer with 8 cores and 72 GB of memory. The exciter was a dipole placed 2 microns from the inner wall and the simulation time was 105 fs. The layer is too thin to be accurately simulated in a reasonable timeframe, but the layer is not crucial for simply visualizing the resonant mode fields.
The resulting spectrum shows the star and triangle modes (Fig. 3(a)). A CW simulation was performed on a single, narrow mode at 610.97 nm (one of the “black dotted modes in Fig. 3(a)). The resulting spatial intensity distribution was clearly consistent with a star mode (Fig. 3(b)) that circles three times before returning to its starting point. While the simple geometric calculation assumes a one-cycle closed path, a large number of related modes can clearly also exist and their strength depends on the position and orientation of the excitation dipole. By changing the refractive index of the inner medium, the sensitivity of both mode types were determined. The sensitivity was 67 nm/RIU (refractive index unit) for the star mode and 863 nm/RIU for the triangle mode in Fig. 3. These values are consistent with those calculated from the geometric equations for the two mode classes.
Fig. 3. (a) Simulated FDTD spectra for a capillary of radii r = 125 and R = 160 µm for two different refractive indices in the channel (1.3300 vs. 1.3303). The star modes are marked by the black dots, and the triangle mode envelopes are represented by the Gaussian fits as shown by the blue and purple lines and described by the mean value, µ. (b) A star mode resonance at a wavelength of 610.97 nm. The blue lines represent the ray diagrams shown in Fig. 2, while the corresponding field intensities are shown on a scale from light green to black.
4. Results and discussion
The FDTD results described above clearly identified the star and triangle modes, producing results that were consistent with the theoretical sensitivity of the various mode types. The geometric analysis was extended to account for the presence of a surface layer on the channel wall. The star modes are expected to redshift while the triangle modes will subdivide into two types whose resonant wavelengths shift in opposite directions.
The lasing mode spectrum for a bare capillary with an rhB solution (Experimental Step 2; Fig. 4) consists of a set of narrowly-spaced modes separated by ∼0.28 nm underneath a more widely-spaced envelope that, together, formed groups of resonances similar to those reported previously [35]. The lasing threshold was ∼6.5 µJ/mm2. The FSR of the narrowly-spaced modes agreed well with the star modes of Eq. (1) (0.28 nm), but for the triangle modes the experimental FSR was ∼2.5 nm, which is about half the expected value for a single mode family with u = v = 1 in Eq. (2). This suggests that we observe multiple “orders” of triangle modes with different numbers of reflections inside the capillary wall (i.e., different u and v parameters), as well as the presence of Type 1 and Type 2 triangle modes.
Fig. 4. The lasing spectra of the initial blank capillary (Experimental Step 2), after PE trilayer deposition (Step 6) and after PS microsphere binding on the PE trilayer (Step 8).
The mode spectrum shifted after deposition of the polyelectrolyte tri-layer and again after the PS microsphere binding (Fig. 4; Experimental steps 6 and 8). Since the spectrum consists of a complicated set of overlapping mode families that are expected to shift in different directions, visually tracking the shifts is difficult. The shift of the envelope function (i.e., one the triangle modes) can, however, be visualized by taking the peaks of the underlying star modes and fitting them to a Gaussian function (Fig. 5), in which a shift of the envelope after each step becomes more apparent. The mode shown is therefore most likely a blueshifting triangle mode of Type 2.
Fig. 5. Zoom-in of part of the emission spectrum after the synthesis steps shown in the legend. The triangle modes (blue lines) are found by Gaussian fits of the star mode maxima.
In order to create a sensorgram of the lasing mode response, Fourier shift theorem [42] was used to track the wavelength shifts. This method measures the phase shift of selected Fourier components, weighted proportionally to their power. For a theoretical mode spacing of 0.27 and 5.8 nm for the star and triangle modes, the corresponding Fourier components in the spectrum are expected to be near 160 and 15, respectively. We therefore took these Fourier components and tracked their phase shifts over a multilayer deposition sequence (Fig. 6). Here, we first examine the PE layer deposition by building three PAH-PSS bilayers – that is, steps 1-2, (3-4-6), (3-4-6), (3-4-6), with the sensorgram measurements done at step 2 and steps 6. A well-defined sensorgram results, in which the star modes slightly redshift as predicted by the theory in the previous section, and the triangle modes showed a large blueshift consistent with the presence of Type 2 modes. Type 1 triangle modes were also present in the spectrum and could be identified by selecting slightly different Fourier components which yielded the expected redshifts.
Fig. 6. (a) Discrete Fourier transform of the spectrum of a capillary with 125-µm inner radius and 160-µm outer radius with PAH-PSS bilayers. The red and orange Fourier components indicate the phases used to calculate the wavelength shift of the triangle modes and star modes, respectively. (b) Corresponding sensorgram for 1-bilayer, 2-bilayers and 3-bilayers of PE functionalization.
The layer thickness can be extrapolated by comparing the magnitude of the mode shift to the geometric theory in the previous section. The refractive indices of the PE bilayers are not well known but have been estimated to be around 1.5 [43,44]. Using this refractive index, a single bilayer needs to be ∼20 nm thick to generate the observed shift. This is a reasonable value given the high saline concentration used to form the PE layers [45].
We next ran a full sensing experiment following all the steps in the experimental section, monitoring the star modes and Type 2 triangle modes in the sensorgram (Fig. 7(a)). The measurements were performed in steps 2, 6, and 8. Once again, there is a stable sensorgram with clear shifts in the expected directions. For a PE trilayer deposition, the star modes shifted by 34 pm, and a further 81 pm subsequent to the microsphere solution being pumped into the channel (note that all measurements – steps 2, 6, and 8 – are done with only the rhB solution). For the triangle modes, we observed a blueshift of –0.47 and a further –0.68 nm in Steps 6 and 8, respectively.
Fig. 7. (a) Sensorgram showing the Type-2 triangle (red points) and star (orange points) mode shifts after the PE bilayer and subsequent microsphere binding. The inset shows a representative HIM image of a group of microspheres bound to the surface. The overall surface coverage was 22%. (b) Sensorgram for a “blank” run in which the PE trilayer was not deposited (red points indicate star and blue points indicate triangle modes). A small shift was observed, suggesting that some microspheres can bind non-specifically to the capillary wall. The inset shows a representative HIM image, in which a few microspheres can indeed be found in the capillary channel. The error bars represent the standard deviation of the data in each section.
Binding of the microspheres produced well-defined mode shifts in the sensorgram (Fig. 7(a)). While the randomly-distributed microspheres might be expected to have a complicated effect by causing scattering losses and changing the ray paths in arbitrary directions, the sensorgram nevertheless showed clear, stable mode shifts after microsphere binding. Qualitatively, the overall effect of the microspheres would be to increase the path length of the star modes, since the rays are more likely to travel through high-index (n = 1.59) polystyrene than otherwise. A similar qualitative argument implies a further blueshift for the Type 2 triangle modes, as observed experimentally.
A blank run was also conducted to see if the microspheres had bound specifically to the functionalized capillary surface. The same steps were repeated as before, except the PE functionalization was left out (Steps 3-5). A small shift was still observed (approx. 5 pm for star modes and –80 pm for the Type 2 triangle modes), suggesting that there is ∼8% nonspecific binding, as estimated from the magnitude of the mode shifts. The HIM micrographs showed that an ∼ 22% microsphere surface coverage on the functionalized capillaries, whereas only a few microspheres could be found on the blank (see Fig. 7 (insets)).
In order to determine the detection limits for these capillary microlaser sensors, the experiments were repeated with microsphere concentrations ranging from 0.05 to 2 mg/mL (corresponding to a molar concentration range of 1.2 to 48.3 nM). In every case, the capillaries were first PE functionalized (Step 5) the lasing modes were measured (Step 6), the microspheres were pumped through the capillary for 30 minutes (Step 7), and then the mode positions were measured again (Step 8). The functionalization steps were the same in every case and resulted in similar lasing mode shifts for both the star and triangle modes (Fig. 8(a)).
Fig. 8. (a) Sensorgrams showing the mode shifts after exposure to the PE tri-layer and a subsequent PS microsphere binding step, using 0.05 mg/mL (purple), 0.5 mg/mL (blue), 1 mg/mL (yellow) and 2 mg/mL (red) microsphere solutions. (b) Plot of the magnitude of the total Type-2 triangle mode shifts after PS binding, as a function of the concentrations of 50 nm PS microsphere solution. The slope yields a sensitivity of 15 pm/nM. The error bars in (a) and (b) represent the standard deviation of the data for the four different concentrations.
The shifts after microsphere binding varied monotonically with the concentration. The sensitivity was estimated by a linear fit of the wavelength shift as a function of the microsphere concentration (Fig. 5(b)), yielding a sensitivity of S = 15 pm/nM for 50-nm-diameter PS microspheres. To obtain the detection limit (DL), the wavelength resolution (Re = 15 pm) was defined as 3 times the largest standard deviation of shifts observed under steady-state conditions in Fig. 8(a). This yielded a detection limit of DL = Re/S = 9.75 nM or 0.41 µg/mL for these lasing capillary sensors with 50-nm PS microspheres. While these values are technically only comparable for the same analytes, the DL is similar to those for capillary-based WGMs in the literature [23] while providing a more robust sensor with much easier synthesis. This number could likely be increased, for example, by combining data from mode shifts of opposite sense, obtaining a better signal-to-noise ratio by using a higher average power of the pump laser (which was ∼0.6 mW in this work), and by minimization of mechanical vibration via better device packaging, as has been recently shown for delicate WGM-type sensors [22].
Additionally, lasing intensity or threshold measurements can be even more sensitive than the lasing model shift measurements reported here [46]. However, intensity-based measurements are sensitive to photobleaching or other instabilities in the lasing gain medium as well as fluctuations in the excitation, and can require a laborious or time-consuming data collection routines.
5. Conclusions
This work developed the concept of the geometric capillary resonances for specific surface sensing. We first developed the theory for the geometric modes in a layered capillary, and showed that the mode structure becomes significantly more complicated due to the formation of new ray paths in the capillary walls. We then built and tested a lasing device in which polyelectrolyte multilayers were deposited on the capillary channel, followed by the amide bonding of carboxy-functionalized PS microspheres as a proof-of-concept system. Good sensorgrams could be obtained by a Fourier analysis of the lasing mode shifts. The magnitude and direction of the shifts were consistent with the theoretical analysis. These resonances offer an intriguing alternative to fluorescent WGM-based sensing schemes with several specific advantages. Since the resonances are defined by lasing modes, the emission intensity is much stronger than for WGMs, and since the lasing medium is continually refreshed, the emission is stable indefinitely (i.e., no bleaching was observed). The bulk sensitivities are higher than for conventional WGMs and they show good response to surface binding, with the shifts of the triangle modes on the order of 0.7 nm after 22% sphere surface coverage.
Funding
Natural Sciences and Engineering Research Council of Canada (463990-2015); National Natural Science Foundation of China (11404052, 11474048, 11874102); Sichuan Province Science and Technology Support Program (2019YJ0187); Graduate School, Technische Universität München; Future Energy Systems.
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