Ultrasensitive optofluidic coupled Fabry-Perot capillary sensors.

Refractive index (RI) measurements are pertinent in concentration and biomolecular detection. Accordingly, an ultrasensitive optofluidic coupled Fabry-Perot (FP) capillary sensor based on the Vernier effect for RI sensing is proposed. Square capillaries integrated with the coupled FP microcavity provide multiple microfluidic channels while reducing the complexity of the fabrication process. The incoherent light source and spectrometer used during measurement facilitate the development of a low-cost sensing system. An ultrahigh RI sensitivity of 51709.0 nm/RIU and detection limit of 2.84 × 10-5 RIU are experimentally demonstrated, indicating acceptable RI sensing performance. The proposed sensor has significant potential for practical and low-cost applications such as RI, concentration, or biomolecular sensing.

Tunable optofluidic microbubble lens.

Optofluidic microlenses are one of the crucial components in many miniature lab-on-chip systems. However, many optofluidic microlenses are fabricated through complex micromachining and tuned by high-precision actuators. We propose a kind of tunable optofluidic microbubble lens that is made by the fuse-and-blow method with a fiber fusion splicer. The optical focusing properties of the microlens can be tuned by changing the refractive index of the liquid inside. The focal spot size is 2.8 µm and the focal length is 13.7 µm, which are better than those of other tunable optofluidic microlenses. The imaging capability of the optofluidic microbubble lens is demonstrated under a resolution test target and the imaging resolution can reach 1 µm. The results indicate that the optofluidic microbubble lens possesses good focusing properties and imaging capability for many applications, such as cell counting, optical trapping, spatial light coupling, beam shaping and imaging.

Hyperboloid-Drum Microdisk Laser Biosensors for Ultrasensitive Detection of Human IgG.

Whispering gallery mode (WGM) microresonators have been used as optical sensors in fundamental research and practical applications. The majority of WGM sensors are passive resonators that require complex systems, thereby limiting their practicality. Active resonators enable the remote excitation and collection of WGM-modulated fluorescence spectra, without requiring complex systems, and can be used as alternatives to passive microresonators. This paper demonstrates an active microresonator, which is a microdisk laser in a hyperboloid-drum (HD) shape. The HD microdisk lasers are a combination of a rhodamine B-doped photoresist and a silica microdisk. These HD microdisk lasers can be utilized for the detection of label-free biomolecules. The biomolecule concentration can be as low as 1 ag mL-1 , whereas the theoretical detection limit of the biosensor for human IgG in phosphate buffer saline is 9 ag mL-1 (0.06 aM ). Additionally, the biosensors are able to detect biomolecules in an artificial serum, with a theoretical detection limit of 9 ag mL-1 (0.06 aM ). These results are approximately four orders of magnitude more sensitive than those for the typical active WGM biosensors. The proposed HD microdisk laser biosensors show enormous detection potential for biomarkers in protein secretions or body fluids.

Optofluidic microbubble Fabry-Pérot cavity.

An optofluidic microbubble Fabry-Pérot (OMBFP) cavity was investigated. In contrast to plane-plane FP (PPFP) cavities, the optical mode confinement and stability in an OMBFP were significantly enhanced. The optical properties of the OMBFP cavity, including the quality (Q) factor, effective mode area, mode distribution as a function of the core refractive index, microbubble position, and mirror tilt angle, were investigated systematically using the finite element method. In optofluidic lasing experiments, a low lasing threshold of 1.25 µJ/mm2, which was one order magnitude lower than that of the PPFP, was achieved owing to improved modal lateral confinement. Since the microbubble acts as a micro-lens and microfluidic channel in the parallel FP cavity, mode selection and cell-dye laser were easily realized in the OMBFP cavity.

High-Q guided mode resonance sensors based on shallow sub-wavelength grating structures.

We present a systematic investigation on the enhancement of the quality (Q) factors for guided-mode resonance (GMR) sensors with shallow subwavelength grating structures. By introducing the coupled-mode model, a theoretical high-Q factor can be achieved by choosing the proper geometric structure. Based on this method, a GMR sensor with a Q factor up to 8000, which is an order of magnitude larger than those of typical GMR sensors with Q factors within 100 ∼ 300, was demonstrated experimentally. Besides, the approached GMR sensor achieved a bulk sensitivity of 135 nm RIU-1 with a high signal to noise ratio, which supports a detection limit of 1 ng ml-1 for bovine serum albumin detection. This high performance GMR sensor paves the way towards high-throughput industrial mass production, and shows great potential for other applications, such as optical filters, spectrometer, and bio-imaging.

Ultra-sensitive biomolecular detection by external referencing optofluidic microbubble resonators.

We propose an effective method for biomolecular detection based on an external referencing optofluidic microbubble resonator system (EROMBRS), which possesses good long-term stability and low noise. In this study, EROMBRSs were used for nonspecific detection of bovine serum albumin (BSA) molecules and specific detection of D-biotin molecules. Ultra-low practical detection limits of 1 fg/mL for nonspecific and specific biomolecular detection were achieved.

Packaged microbubble resonator optofluidic flow rate sensor based on Bernoulli Effect.

A novel flow sensor based on dynamic fluid pressure changing in a packaged microbubble resonator without additional modification on its structure has been proposed and experimentally demonstrated. The results of sensing performance under both tunable laser source and broadband light source are presented. The flow rate sensitivity can reach up to 0.0196 pm / (µL/min). The fluid pressure variation caused by Bernoulli Effect is also analyzed theoretically.

Symmetric guided-mode resonance sensors in aqueous media with ultrahigh figure of merit.

Optical sensors with a high figure of merit (FOM) for refractive index measurement can substantially enhance detection performance. For guided mode resonance (GMR) sensors, previous works mainly focused on the sensitivity enhancement rather than FOM optimization; therefore, the state-of-the-art FOM is limited within the range of 100. To address this, we propose a low-index, ultraviolet-curable resin (n = 1.344) to form a simple, stable, symmetric, GMR sensor, with enhanced sensitivity, narrowed resonant linewidth, and substantially improved FOM, in aqueous media. The influence of structural parameters was systematically investigated, and optimized FOM values as high as tens of thousands were obtained using numerical calculation. Using low-cost, nanoimprinting technology, we experimentally demonstrated a spectral linewidth as narrow as 56 pm, a bulk refractive index sensitivity of 233.35 nm / RIU, and a low detection limit 1.93 × 10-6, resulting in a FOM value up to 4200 (48 times typical GMR sensors). The proposed symmetric GMR sensor exhibits great potential in a variety of applications, including label-free biosensing, bio-imaging, and optical filters.

Design for Distributed Feedback Laser Biosensors Based on the Active Grating Model.

The distributed feedback (DFB) laser is widely used in sensing because of its portable size, simple fabrication and high sensitivity. Most theoretical design models are based on passive Bragg gratings. However, passive grating models cannot be used to predict sensor performance using the important indicator of figure of merit (FOM) through theoretical calculations. To solve this problem, we replaced the passive grating with an active grating by using the imaginary part of the coupling constant that represents the value of the gain. As a comparison, the influence of the full width at half maximum (FWHM) and sensitivity were analyzed for different grating duty cycles and depths in the passive grating sensors. To obtain a higher FOM in the active grating sensors, we systematically investigated the effects of duty cycle and gain value through numerical simulations. We found that the redshift caused by a duty cycle increase can improve the sensitivity of biomolecule detection by 1.7 times.

High-Sensitivity Optical Sensors Empowered by Quasi-Bound States in the Continuum in a Hybrid Metal-Dielectric Metasurface.

Enhancing light-matter interaction is a key requisite in the realm of optical sensors. Bound states in the continuum (BICs), possessing high quality factors (Q factors), have shown great advantages in sensing applications. Recent theories elucidate the ability of BICs with hybrid metal-dielectric architectures to achieve high Q factors and high sensitivities. However, the experimental validation of the sensing performance in such hybrid systems remains equivocal. In this study, we propose two symmetry-protected quasi-BIC modes in a metal-dielectric metasurface. Our results demonstrate that, under the normal incidence of light, the quasi-BIC mode dominated by dielectric can achieve a high Q factor of 412 and a sensing performance with a high bulk sensitivity of 492.7 nm/RIU (refractive index unit) and a figure of merit (FOM) of 266.3 RIU-1, while the quasi-BIC mode dominated by metal exhibits a stronger surface affinity in the biotin-streptavidin bioassay. These findings offer a promising approach for implementing metasurface-based sensors, representing a paradigm for high-sensitivity biosensing platforms.

An all-optical multidirectional mechano-sensor inspired by biologically mechano-sensitive hair sensilla.

Mechano-sensitive hair-like sensilla (MSHS) have an ingenious and compact three-dimensional structure and have evolved widely in living organisms to perceive multidirectional mechanical signals. Nearly all MSHS are iontronic or electronic, including their biomimetic counterparts. Here, an all-optical mechano-sensor mimicking MSHS is prototyped and integrated based on a thin-walled glass microbubble as a flexible whispering-gallery-mode resonator. The minimalist integrated device has a good directionality of 32.31 dB in the radial plane of the micro-hair and can detect multidirectional displacements and forces as small as 70 nm and 0.9 µN, respectively. The device can also detect displacements and forces in the axial direction of the micro-hair as small as 2.29 nm and 3.65 µN, respectively, and perceive different vibrations. This mechano-sensor works well as a real-time, directional mechano-sensory whisker in a quadruped cat-type robot, showing its potential for innovative mechano-transduction, artificial perception, and robotics applications.

Highly sensitive, modification-free, and dynamic real-time stereo-optical immuno-sensor.

Modification-free biosensing with high specificity and sensitivity is essential for miniaturized, online, integrated, and rapid, or even real-time molecular analyses. However, most optical biosensors are based on surface pre-modification or fluorescent labeling, and have either low sensitivity or low quality factor (Q). To address these difficulties, in this study, an optical sensor prototype was developed with a microbubble optofluidic channel integrated inside a Fabry-Pérot cavity to three-dimensionally tailor the intra-cavity light field via the intra-cavity lensing (microbubble) configuration. A high Q-factor (∼105), small mode volume, and high light energy density were experimentally achieved with this "stereo-sensor" while maintaining an ultrahigh refractive index (RI) sensitivity (679 nm/RIU) and ultra-small RI resolution (∼10-7 RIU at 950 nm). Moreover, specific detection of very low concentration of biomolecules (5 fg/mL for human IgG and 0.5 pg/mL for human serum albumin (HSA)) and wide range of protein concentrations (e.g., fg/mL-ng/mL for human IgG and pg/mL-ng/mL for HSA) without probe pre-modification were achieved owing to the RI change specifically associated with the probe-target binding and the corresponding bio-macromolecular conformation change. This modification-free stereosensing scenario is applicable to continuous, real-time, and multiplexed operations, thus showing potential for online, integrated, dynamic, biomolecular analyses in vitro or in vivo, such as the dynamic metabolic analysis of single cells or organoids and point-of-care tests.

Optical Whispering-Gallery-Mode Microbubble Sensors.

Whispering-gallery-mode (WGM) microbubble resonators are ideal optical sensors due to their high quality factor, small mode volume, high optical energy density, and geometry/design/structure (i.e., hollow microfluidic channels). When used in combination with microfluidic technologies, WGM microbubble resonators can be applied in chemical and biological sensing due to strong light-matter interactions. The detection of ultra-low concentrations over a large dynamic range is possible due to their high sensitivity, which has significance for environmental monitoring and applications in life-science. Furthermore, WGM microbubble resonators have also been widely used for physical sensing, such as to detect changes in temperature, stress, pressure, flow rate, magnetic field and ultrasound. In this article, we systematically review and summarize the sensing mechanisms, fabrication and packing methods, and various applications of optofluidic WGM microbubble resonators. The challenges of rapid production and practical applications of WGM microbubble resonators are also discussed.

Label-Free Bound-States-in-the-Continuum Biosensors.

Bound states in the continuum (BICs) have attracted considerable attentions for biological and chemical sensing due to their infinite quality (Q)-factors in theory. Such high-Q devices with enhanced light-matter interaction ability are very sensitive to the local refractive index changes, opening a new horizon for advanced biosensing. In this review, we focus on the latest developments of label-free optical biosensors governed by BICs. These BICs biosensors are summarized from the perspective of constituent materials (i.e., dielectric, metal, and hybrid) and structures (i.e., grating, metasurfaces, and photonic crystals). Finally, the current challenges are discussed and an outlook is also presented for BICs inspired biosensors.

Label-free detection of cardiac troponin-I with packaged thin-walled microbubble resonators.

The measurement of cardiac troponin-I (cTnI) is widely used for diagnosing acute myocardial infarction (AMI) diseases because of its myocardial specificity. Packaged microbubble resonators with thin wall are utilized for label-free and specific detection of cTnI based on whispering gallery mode (WGM). This packaged structure can provide a good protection for the biosensor, improve the anti-interference ability of the sensor and reduce the system noise. The theoretical detection limit of the biosensors for cTnI in phosphate buffer saline (PBS) is 0.4 ag mL-1 (0.02 aM ). Furthermore, we demonstrated that the biosensors can be used to detect cTnI molecules in simulated serum and the theoretical detection limit is also 0.4 ag mL-1 (0.02 aM ). These results are much far below the clinical cut-off value and show a huge application potential for the detection of cardiac biomarkers of AMI.

Guided Mode Resonance Sensors with Optimized Figure of Merit.

The guided mode resonance (GMR) effect is widely used in biosensing due to its advantages of narrow linewidth and high efficiency. However, the optimization of a figure of merit (FOM) has not been considered for most GMR sensors. Aimed at obtaining a higher FOM of GMR sensors, we proposed an effective design method for the optimization of FOM. Combining the analytical model and numerical simulations, the FOM of "grating-waveguide" GMR sensors for the wavelength and angular shift detection schemes were investigated systematically. In contrast with previously reported values, higher FOM values were obtained using this method. For the "waveguide-grating" GMR sensors, a linear relationship between the grating period and groove depth was obtained, which leads to excellent FOM values for both the angular and wavelength resonance. Such higher performance GMR sensors will pave the way to lower detection limits in biosensing.

Spectral Modulation of Optofluidic Coupled-Microdisk Lasers in Aqueous Media.

We present the spectral modulation of an optofluidic microdisk device and investigate the mechanism and characteristics of the microdisk laser in aqueous media. The optofluidic microdisk device combines a solid-state dye-doped polymer microdisk with a microfluidic channel device, whose optical field can interact with the aqueous media. Interesting phenomena, such as mode splitting and single-mode lasing in the laser spectrum, can be observed in two coupled microdisks under the pump laser. We modulated the spectra by changing the gap of the two coupled microdisks, the refractive indices of the aqueous media, and the position of a pump light, namely, selective pumping schemes. This optofluidic microlaser provides a method to modulate the laser spectra precisely and flexibly, which will help to further understand spectral properties of coupled microcavity laser systems and develop potential applications in photobiology and photomedicine.

Highly Sensitive Label-Free Detection of Small Molecules with an Optofluidic Microbubble Resonator.

The detection of small molecules has increasingly attracted the attention of researchers because of its important physiological function. In this manuscript, we propose a novel optical sensor which uses an optofluidic microbubble resonator (OFMBR) for the highly sensitive detection of small molecules. This paper demonstrates the binding of the small molecule biotin to surface-immobilized streptavidin with a detection limit reduced to 0.41 pM. Furthermore, binding specificity of four additional small molecules to surface-immobilized streptavidin is shown. A label-free OFMBR-based optical sensor has great potential in small molecule detection and drug screening because of its high sensitivity, low detection limit, and minimal sample consumption.