Real-time monitoring of hydrogel phase transition in an ultrahigh Q microbubble resonator

Daquan Yang; Aiqiang Wang; Jin-Hui Chen; Xiao-Chong Yu; Chuwen Lan; Yuefeng Ji; Yun-Feng Xiao

doi:10.1364/PRJ.380238

Abstract

The ability to sense dynamic biochemical reactions and material processes is particularly crucial for a wide range of applications, such as early-stage disease diagnosis and biomedicine development. Optical microcavities-based label-free biosensors are renowned for ultrahigh sensitivities, and the detection limit has reached a single nanoparticle/molecule level. In particular, a microbubble resonator combined with an ultrahigh quality factor (

Q

) and inherent microfluidic channel is an intriguing platform for optical biosensing in an aqueous environment. In this work, an ultrahigh

Q

microbubble resonator-based sensor is used to characterize dynamic phase transition of a thermosensitive hydrogel. Experimentally, by monitoring resonance wavelength shift and linewidth broadening, we (for the first time to our knowledge) reveal that the refractive index is increased and light scattering is enhanced simultaneously during the hydrogel hydrophobic transition process. The platform demonstrated here paves the way to microfluidical biochemical dynamic detection and can be further adapted to investigating single-molecule kinetics.

Monitoring and controlling the phase transition dynamics of materials is very important for both fundamental studies and practical applications [1–3], e.g., transformation of matter state, ferromagnetic phase transition, superconductor dynamics, and hydrogel phase transition dynamics. As a crucial phase-transition material, hydrogels are a class of biomaterials with a broad range of applications, such as in biochemistry and biopharmaceutics [4–7]. To monitor the hydrogel phase-transition process, several methods have been developed, including nuclear magnetic resonance (NMR) and rheology. However, the NMR method is with high cost, requires specialized equipment, and is hampered by low resolution in aqueous environments [8]. As for the rheology method, it cannot be easily implemented to study rapid gelling dynamics or mechanically weak materials [9]. On the other hand, optical microcavities of ultrahigh quality factors (Q) and small volumes [10] can significantly enhance light–matter interactions. Therein, whispering gallery mode (WGM) microresonator-based label-free biosensors are renowned for their ultrahigh sensitivities and low detection limit [11–19]. In particular, several WGM microresonator systems have achieved single nanoparticles [20–33], molecules (e.g., viruses, proteins, and DNAs) [34–46], and even atomic ions [47]. However, there have been few demonstrations yet that these systems can be used to investigate the dynamics of biochemical reactions [48].

Herein, real-time monitoring of the hydrogel phase transition (i.e., hydrophilic transition and hydrophobic transition) in WGM microbubble resonator (MBR)-based sensors is first demonstrated by continuously monitoring both wavelength shift and linewidth broadening simultaneously. Experimentally, the thermosensitive hydrogel phase transition is optically controlled by increasing/decreasing the irradiation light power ( $\sim 1550 nm$ ). During a hydrophilic to hydrophobic transition process, an overall wavelength redshift $\sim 40 pm$ and a distinct linewidth broadening over 10 times are observed, respectively. The WGM linewidth broadening unambiguously reveals the hydrogel phase transition due to the enhanced light scattering, and the refractive index changes are detected by monitoring wavelength shift. Note that compared with the wavelength shift sensing mechanism, the WGM linewidth broadening is immune to noises, including thermal noise and laser frequency noise in practical measurements. The results shown in this work demonstrate that optical MBR is a promising platform for further investigating the biochemical dynamics and molecule kinetics [44].

Figure 1.(a) Schematic of the MBR platform for real-time monitoring of the dynamic reactions of hydrogel phase transition. The thermosensitive phase transition of PNIPA is optically controlled by the irradiation light power (

\sim 1550 nm

) from an SMF. (b) Monitoring the phase transition dynamics of the PNIPA solution by tracking the wavelength shift and linewidth broadening of a WGM. Insets, CCD images of the microbubble with the PNIPA solution at hydrophilic and hydrophobic state, respectively. (c) Transmission spectrum of MBR with the PNIPA solution at hydrophilic state. The enlarged view of the red square region is shown in (d). (e) Typical optical field distribution of a WGM in the MBR by finite-element method simulation.

As shown in Fig. 1(a), a tunable laser (Newport, TLB-6712) at 780-nm wavelength band is used to efficiently excite the WGMs of the MBR via fiber–taper coupling. A fiber polarization controller is adjusted manually to control the polarization of the input laser and achieve the maximum light coupling efficiency. The transmission light signal is collected and detected in real time by a low-noise photodetector (New Focus, 1801-FC) and analyzed by an oscilloscope. To demonstrate the ultrahigh $Q$ factor of the WGMs of the MBR, the MBR is coupled with the optical microfiber through the evanescent field, and there is no contact between the MBR and fiber. A representative transmission spectrum of a typical MBR filled with the PNIPA solution is shown in Fig. 1(c). Although the absorption of the PNIPA solution to the probe light can spoil the $Q$ factors of the microbubble cavity, the corresponding mode still possesses an ultrahigh $Q$ factor of $9.11 \times 10^{7}$ , as shown in Fig. 1(d). This is mainly due to the relatively small field distribution of WGMs inside the PNIPA solution, as shown in Fig. 1(e). Remarkably, as depicted in Fig. 1(b), the reaction dynamics (i.e., phase transition including hydrophilic transition and hydrophobic transition) of the PNIPA is monitored continuously by real-time tracking of the wavelength shift and linewidth broadening when the control power of the irradiation light changes. As the control power increases, the WGMs exhibit redshift and linewidth broadening during the hydrophobic transition process. Conversely, as the control power decreases, the WGMs exhibit blueshift and linewidth narrowing during the hydrophilic transition process.

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Figure 2.Transmission evolution of the microbubble with the PNIPA hydrogel when the control power of the irradiation light first (a) increases from 0 to 3.00 mW, and then (b) decreases from 3.00 to 0 mW; (c) CCD images of a cycle of phase-transition process of the PNIPA hydrogel. The microbubble changes from transparent hydrophilic state to opaque hydrophobic state due to the increased scattering. Inset, the scale bar is 125 μm.

Figure 3.(a) WGM wavelength shifts and (b) linewidth broadenings as a function of control power of the irradiation light from 0 to 3.00 mW, when the MBRs are filled with air (blue line with triangular marker), DI water (black line with square marker), and PNIPA hydrogel (red line with circular marker). Compared with the result of microbubble cavities filled with air and DI water, note that a hydrophilic to hydrophobic transition process of PNIPA can be clarified as four stages: (i) pure hydrophilic state (0–1.44 mW); (ii) subtransition state (1.44–2.04 mW); (iii) transition state (2.04–2.52 mW); (iv) pure hydrophobic state (

> 2.52 mW

Figure 4.(a) Real-time WGM resonance wavelength shift and (b) linewidth broadening during the PNIPA hydrogel phase transition (a hydrophilic to hydrophobic transition) monitored by an MBR. The control power of the irradiation light is switched on at

\sim 12.5 s

. During the whole phase-transition process, a small blueshift of 8.02 pm in wavelength is first observed within 13.22–15.62 s; then the overall redshift of the resonance wavelength is 39.23 pm, and the maximized linewidth broadening is 3.96 GHz.

In summary, we experimentally characterize the thermosensitive PNIPA hydrogel phase transition via an ultrahigh Q MBR sensor. By controlling the output power of the irradiation light, the optical tuning of the PNIPA hydrogel phase transition has been successfully achieved. Furthermore, we reveal the refractive index and temperature changes during the different stages of the phase transition process by monitoring the wavelength shift and linewidth broadening in real time. Our work demonstrates that MBR-based biosensors are promising for further quantitatively investigating the energy change during a phase transition, thus providing insights into their dynamic reaction mechanisms.

Acknowledgment. The authors thank Qi-Tao Cao, Shui-Jing Tang, and Pei-Ji Zhang for helpful discussions.