Submonolayer biolasers for ultrasensitive biomarker detection.

Biomarker detection is key to identifying health risks. However, designing sensitive and single-use biosensors for early diagnosis remains a major challenge. Here, we report submonolayer lasers on optical fibers as ultrasensitive and disposable biosensors. Telecom optical fibers serve as distributed optical microcavities with high Q-factor, great repeatability, and ultralow cost, which enables whispering-gallery laser emission to detect biomarkers. It is found that the sensing performance strongly depends on the number of gain molecules. The submonolayer lasers obtained a six-order-of-magnitude improvement in the lower limit of detection (LOD) when compared to saturated monolayer lasers. We further achieve an ultrasensitive immunoassay for a Parkinson's disease biomarker, alpha-synuclein (α-syn), with a lower LOD of 0.32 pM in serum, which is three orders of magnitude lower than the α-syn concentration in the serum of Parkinson's disease patients. Our demonstration of submonolayer biolaser offers great potentials in high-throughput clinical diagnosis with ultimate sensitivity.

Phase-Transition Microcavity Laser.

Liquid-crystal microcavity lasers have attracted considerable attention because of their extraordinary tunability and sensitive response to external stimuli, and because they operate generally within a specific phase. Here, we demonstrate a liquid-crystal microcavity laser operated in the phase transition in which the reorientation of liquid-crystal molecules occurs from aligned to disordered states. A significant wavelength shift of the microlaser is observed, resulting from the dramatic changes in the refractive index of liquid-crystal microdroplets during the phase transition. This phase-transition microcavity laser is then exploited for sensitive thermal sensing, enabling a two-order-of-magnitude enhancement in sensitivity compared with the nematic-phase microlaser operated far from the transition point. Experimentally, we demonstrate an exceptional sensitivity of -40 nm/K and an ultrahigh resolution of 320 µK. The phase-transition microcavity laser features compactness, softness, and tunability, showing great potential for high-performance sensors, optical modulators, and soft matter photonics.

Dissipative Acousto-optic Interactions in Optical Microcavities.

We propose and demonstrate experimentally the strong dissipative acousto-optic interaction between a suspended vibrating microfiber and a whispering-gallery microcavity. On the one hand, the dissipative response driven by an external stimulus of acoustic waves is found to be stronger than the dispersive response by 2 orders of magnitude. On the other hand, dead points emerge with the zero dissipative response at certain parameters, promising the potentials in physical sensing such as precise measurements of magnetic field and temperature. The strong dissipative acousto-optic interaction is then explored for ultrasensitive detection of broadband acoustic waves. A noise equivalent pressure as low as 0.81 Pa at 140 kHz in air is demonstrated experimentally, insensitive to cavity Q factors and does not rely on mechanical resonances.

Single-molecule optofluidic microsensor with interface whispering gallery modes.

Label-free sensors are highly desirable for biological analysis and early-stage disease diagnosis. Optical evanescent sensors have shown extraordinary ability in label-free detection, but their potentials have not been fully exploited because of the weak evanescent field tails at the sensing surfaces. Here, we report an ultrasensitive optofluidic biosensor with interface whispering gallery modes in a microbubble cavity. The interface modes feature both the peak of electromagnetic-field intensity at the sensing surface and high-Q factors even in a small-sized cavity, enabling a detection limit as low as 0.3 pg/cm2 The sample consumption can be pushed down to 10 pL due to the intrinsically integrated microfluidic channel. Furthermore, detection of single DNA with 8 kDa molecular weight is realized by the plasmonic-enhanced interface mode.

1/f-noise-free optical sensing with an integrated heterodyne interferometer.

Optical evanescent sensors can non-invasively detect unlabeled nanoscale objects in real time with unprecedented sensitivity, enabling a variety of advances in fundamental physics and biological applications. However, the intrinsic low-frequency noise therein with an approximately 1/f-shaped spectral density imposes an ultimate detection limit for monitoring many paramount processes, such as antigen-antibody reactions, cell motions and DNA hybridizations. Here, we propose and demonstrate a 1/f-noise-free optical sensor through an up-converted detection system. Experimentally, in a CMOS-compatible heterodyne interferometer, the sampling noise amplitude is suppressed by two orders of magnitude. It pushes the label-free single-nanoparticle detection limit down to the attogram level without exploiting cavity resonances, plasmonic effects, or surface charges on the analytes. Single polystyrene nanobeads and HIV-1 virus-like particles are detected as a proof-of-concept demonstration for airborne biosensing. Based on integrated waveguide arrays, our devices hold great potentials for multiplexed and rapid sensing of diverse viruses or molecules.

Laser particles with omnidirectional emission for cell tracking.

The ability to track individual cells in space over time is crucial to analyzing heterogeneous cell populations. Recently, microlaser particles have emerged as unique optical probes for massively multiplexed single-cell tagging. However, the microlaser far-field emission is inherently direction-dependent, which causes strong intensity fluctuations when the orientation of the particle varies randomly inside cells. Here, we demonstrate a general solution based on the incorporation of nanoscale light scatterers into microlasers. Two schemes are developed by introducing either boundary defects or a scattering layer into microdisk lasers. The resulting laser output is omnidirectional, with the minimum-to-maximum ratio of the angle-dependent intensity improving from 0.007 (-24 dB) to > 0.23 (-6 dB). After transfer into live cells in vitro, the omnidirectional laser particles within moving cells could be tracked continuously with high signal-to-noise ratios for 2 h, while conventional microlasers exhibited frequent signal loss causing tracking failure.

Nonlinear Sensing with Whispering-Gallery Mode Microcavities: From Label-Free Detection to Spectral Fingerprinting.

Optical microresonators have attracted intense interests in highly sensitive molecular detection and optical precision measurement in the past decades. In particular, the combination of a high quality factor with a small mode volume significantly enhances the nonlinear light-matter interaction in whispering-gallery mode (WGM) microresonators, which greatly boost nonlinear optical sensing applications. Nonlinear WGM microsensors not only allow for label-free detection of molecules with an ultrahigh sensitivity but also support new functionalities in sensing such as the specific spectral fingerprinting of molecules with frequency conversion involved. Here, we review the mechanisms, sensing modalities, and recent progresses of nonlinear optical sensors along with a brief outlook on the possible future research directions of this rapidly advancing field.

Microcavity Nonlinear Optics with an Organically Functionalized Surface.

We report enhanced optical nonlinear effects at the surface of an ultrahigh-Q silica microcavity functionalized by a thin layer of organic molecules. The maximal conversion efficiency of third harmonic generation reaches ∼1680%/W^{2} and an absolute efficiency of 0.0144% at pump power of ∼2.90 mW, which is approximately 4 orders of magnitude higher than that in a reported silica microcavity. Further analysis clarifies the elusive dependence of the third harmonic signal on the pump power in previous literature. Molecule-functionalized microcavities may find promising applications in high-efficiency broadband optical frequency conversion and offer potential in sensitive surface analysis.

A Tunable Optofluidic Microlaser in a Photostable Conjugated Polymer.

The optofluidic laser has become an important platform for biological sensing and medical diagnosis. To date, fluorescent dyes and proteins have been widely utilized as gain materials for biological analysis due to their good biocompatibility, but the limited photostability restricts their reliability and sensitivity. Here, an optofluidic microlaser with an ultralow threshold down to 7.8 µJ cm-2 in the ultrahigh-Q whispering-gallery microcavity, which is filled with a biocompatible conjugated polymer, is demonstrated. This conjugated polymer exhibits a significant enhancement in the lasing stability compared with a typical laser dye (Nile red). In the experiment, after 20 min of illumination with the excitation intensity of 23.2 MW cm-2 , the lasing intensity of the conjugated polymer experiences a decrease of less than 10%, while the lasing feature of Nile red completely disappears. Additionally, by mechanically stretching the resonator, the lasing frequency can be fine-tuned with the range of about 2 nm, exceeding the free spectral range of the resonator.

On-Chip Spiral Waveguides for Ultrasensitive and Rapid Detection of Nanoscale Objects.

Ultrasensitive and rapid detection of nano-objects is crucial in both fundamental studies and practical applications. Optical sensors using evanescent fields in microcavities, plasmonic resonators, and nanofibers allow label-free detection down to single molecules, but practical applications are severely hindered by long response time and device reproducibility. Here, an on-chip dense waveguide sensor to monitor single unlabeled nanoparticles in a strong optical evanescent field is demonstrated. The spiral nanowaveguide design enables two orders of magnitude enhancement in sensing area compared to a straight waveguide, significantly improving the particle capture ability and shortening the target analysis time. In addition, the measurement noise is suppressed to a level of 10-4 in the transmitted power, pushing the detection limit of single particles down to the size of 100 nm. The waveguide sensor on the silicon-on-isolator platform can be fabricated reproducibly by the conventional semiconductor processing and compatible with surface functionalization chemistries and microfluidics, which could lead to widespread use for sensing in environmental monitoring and human health.

Optically sizing single atmospheric particulates with a 10-nm resolution using a strong evanescent field.

Although an accurate evaluation of the distribution of ultrafine particulate matter in air is of utmost significance to public health, the usually used PM2.5 index fails to provide size distribution information. Here we demonstrate a low-profile and cavity-free size spectrometer for probing fine and ultrafine particulate matter by using the enhanced particle-perturbed scattering in strong optical evanescent fields of a nanofiber array. The unprecedented size resolution reaches 10 nm for detecting single 100-nm-diameter nanoparticles by employing uniform nanofibers and controlling the polarizations of the probe light. This size spectrometry was tested and used to retrieve the size distribution of particulate matter in the air of Beijing, yielding mass concentrations of nanoparticles, as a secondary exercise, consistent with the officially released data. This nanofiber-array probe shows potential for the full monitoring of air pollution and for studying early-stage haze evolution and can be further extended to explore nanoparticle interactions.