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 (∼1550nm). During a hydrophilic to hydrophobic transition process, an overall wavelength redshift ∼40pm 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].

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 9.11×107, 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.

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.