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.

Ultrahigh Passive Cooling Power in Hydrogel with Rationally Designed Optofluidic Properties.

The cooling power of a radiative cooler is more than halved in the tropics, e.g., Singapore, because of its harsh weather conditions including high humidity (84% on average), strong downward atmospheric radiation (∼40% higher than elsewhere), abundant rainfall, and intense solar radiation (up to 1200 W/m2 with ∼58% higher UV irradiation). So far, there has been no report of daytime radiative cooling that well achieves effective subambient cooling. Herein, through integrated passive cooling strategies in a hydrogel with desirable optofluidic properties, we demonstrate stable subambient (4-8 °C) cooling even under the strongest solar radiation in Singapore. The integrated passive cooler achieves an ultrahigh cooling power of ∼350 W/m2, 6-10 times higher than a radiative cooler in a tropical climate. An in situ study of radiative cooling with various hydration levels and ambient humidity is conducted to understand the interaction between radiation and evaporative cooling. This work provides insights for the design of an integrated cooler for various climates.

Optofluidic time-stretch imaging flow cytometry with a real-time storage rate beyond 5.9 GB/s.

Optofluidic time-stretch imaging flow cytometry (OTS-IFC) provides a suitable solution for high-precision cell analysis and high-sensitivity detection of rare cells due to its high-throughput and continuous image acquisition. However, transferring and storing continuous big data streams remains a challenge. In this study, we designed a high-speed streaming storage strategy to store OTS-IFC data in real-time, overcoming the imbalance between the fast generation speed in the data acquisition and processing subsystem and the comparatively slower storage speed in the transmission and storage subsystem. This strategy, utilizing an asynchronous buffer structure built on the producer-consumer model, optimizes memory usage for enhanced data throughput and stability. We evaluated the storage performance of the high-speed streaming storage strategy in ultra-large-scale blood cell imaging on a common commercial device. The experimental results show that it can provide a continuous data throughput of up to 5891 MB/s.

Deep Learning Enables Optofluidic Zoom System with Large Zoom Ratio and High Imaging Resolution.

Due to the relatively low optical power of a liquid lens, it is usually difficult to achieve a large zoom ratio and a high-resolution image simultaneously in an optofluidic zoom imaging system. We propose an electronically controlled optofluidic zoom imaging system combined with deep learning, which achieves a large continuous zoom change and a high-resolution image. The zoom system consists of an optofluidic zoom objective and an image-processing module. The proposed zoom system can achieve a large tunable focal length range from 4.0 mm to 31.3 mm. In the focal length range of 9.4 mm to 18.8 mm, the system can dynamically correct the aberrations by six electrowetting liquid lenses to ensure the image quality. In the focal length range of 4.0-9.4 mm and 18.8-31.3 mm, the optical power of a liquid lens is mainly used to enlarge the zoom ratio, and deep learning enables the proposed zoom system with improved image quality. The zoom ratio of the system reaches 7.8×, and the maximum field of view of the system can reach ~29°. The proposed zoom system has potential applications in camera, telescope and so on.

Optofluidic Flow Cytometer with In-Plane Spherical Mirror for Signal Enhancement.

Statistical analysis of the properties of single microparticles, such as cells, bacteria or plastic slivers, has attracted increasing interest in recent years. In this regard, field flow cytometry is considered the gold standard technique, but commercially available instruments are bulky, expensive, and not suitable for use in point-of-care (PoC) testing. Microfluidic flow cytometers, on the other hand, are small, cheap and can be used for on-site analyses. However, in order to detect small particles, they require complex geometries and the aid of external optical components. To overcome these limitations, here, we present an opto-fluidic flow cytometer with an integrated 3D in-plane spherical mirror for enhanced optical signal collection. As a result, the signal-to-noise ratio is increased by a factor of six, enabling the detection of particle sizes down to 1.5 µm. The proposed optofluidic detection scheme enables the simultaneous collection of particle fluorescence and scattering using a single optical fiber, which is crucial to easily distinguishing particle populations with different optical properties. The devices have been fully characterized using fluorescent polystyrene beads of different sizes. As a proof of concept for potential real-world applications, signals from fluorescent HEK cells and Escherichia coli bacteria were analyzed.

Tunable Optical Vortex from a Nanogroove-Structured Optofluidic Microlaser.

Optical vortices with tunable properties in multiple dimensions are highly desirable in modern photonics, particularly for broadly tunable wavelengths and topological charges at the micrometer scale. Compared to solid-state approaches, here we demonstrate tunable optical vortices through the fusion of optofluidics and vortex beams in which the handedness, topological charges, and lasing wavelengths could be fully adjusted and dynamically controlled. Nanogroove structures inscribed in Fabry-Pérot optofluidic microcavities were proposed to generate optical vortices by converting Hermite-Gaussian laser modes. Topological charges could be controlled by tuning the lengths of the nanogroove structures. Vortex laser beams spanning a wide spectral band (430-630 nm) were achieved by alternating different liquid gain materials. Finally, dynamic switching of vortex laser wavelengths in real-time was realized through an optofluidic vortex microlaser device. The findings provide a robust yet flexible approach for generating on-chip vortex sources with multiple dimensions, high tunability, and reconfigurability.

Aerogel-Lined Capillaries for Raman Signal Gain of Aqueous Mixtures.

We report an experimental study on the gain of the Raman signal of aqueous mixtures and liquid water when confined in aerogel-lined capillaries of various lengths of up to 20 cm and various internal diameters between 530 and 1000 µm. The lining was made of hydrophobised silica aerogel, and the carrier capillary body consisted of fused silica or borosilicate glass. Compared to the Raman signal detected from bulk liquid water with the same Raman probe, a Raman signal 27 times as large was detected when the liquid water was confined in a 20 cm-long capillary with an internal diameter of 700 µm. In comparison with silver-lined capillaries of the same length and same internal diameter, the aerogel-lined capillaries featured a superior Raman signal gain and a longer gain stability when exposed to mixtures of water, sugar, ethanol and acetic acid.

Manufacture of Three-Dimensional Optofluidic Spot-Size Converters in Fused Silica Using Hybrid Laser Microfabrication.

We propose a hybrid laser microfabrication approach for the manufacture of three-dimensional (3D) optofluidic spot-size converters in fused silica glass by a combination of femtosecond (fs) laser microfabrication and carbon dioxide laser irradiation. Spatially shaped fs laser-assisted chemical etching was first performed to form 3D hollow microchannels in glass, which were composed of embedded straight channels, tapered channels, and vertical channels connected to the glass surface. Then, carbon dioxide laser-induced thermal reflow was carried out for the internal polishing of the whole microchannels and sealing parts of the vertical channels. Finally, 3D optofluidic spot-size converters (SSC) were formed by filling a liquid-core waveguide solution into laser-polished microchannels. With a fabricated SSC structure, the mode spot size of the optofluidic waveguide was expanded from ~8 µm to ~23 µm with a conversion efficiency of ~84.1%. Further measurement of the waveguide-to-waveguide coupling devices in the glass showed that the total insertion loss of two symmetric SSC structures through two ~50 µm-diameter coupling ports was ~6.73 dB at 1310 nm, which was only about half that of non-SSC structures with diameters of ~9 µm at the same coupling distance. The proposed approach holds great potential for developing novel 3D fluid-based photonic devices for mode conversion, optical manipulation, and lab-on-a-chip sensing.

Reusable optofluidic point-of-care testing platform with lyophilized specific antibody for fluorescence detection of cholylglycine in serum.

A reusable optofluidic point-of-care testing platform (OPOCT) was successfully constructed through integrating evanescent wave fluorescence technology into an all-fiber-based optofluidic system. The compact design of the OPOCT allows it to be portable and suitable for on-site sensitive determination of biomarkers in serum without complicated and costly procedures. The sensitivity of 90.9 pM for antibody determination is observed thanks to the high transmission efficiency of excitation light and fluorescence in the OPOCT. The affinity constant between cholylglycine (CG) and anti-CG antibody was quantified using this platform based on the proposed theory. Using the lyophilized fluorescence-labeled specific antibody and reusable fiber optic biosensor, the OPOCT is applied to the one-step sensitive determination of CG in serum, which eliminates the dearth associated with liquid reagent handling, disposable biosensors, and user intervention. A limit of detection of 0.025 µg/mL for CG is obtained, which is far more than adequate for meeting diagnostic requirements. The matrix effect of serum samples on the evanescent wave-based optofluidic biosensor can be effectively reduced by simple dilution of serum samples. The performance of the OPOCT also compared favorably with that of a commercial turbidimetric inhibition immunoassay through analyzing multiple serum samples. This platform is ready to expand to measure any other biomarker by using its specific antibody. The simplicity, sensitivity, cost-effectiveness, and robustness of the OPOCT enable the early diagnosis of disease and making a timely clinical decision. Graphical abstract .

All-Fiber Measurement of Surface Tension Using a Two-Hole Fiber.

An all-fiber approach is presented to measure surface tension. The experimental realization relies on the use of a specialty fiber, a so-called two-hole fiber (THF), which serves a two-fold purpose: providing a capillary channel to produce bubbles while having the means to measure the power reflected at the end facet of the fiber core. We demonstrate that provided a controlled injection of gas into the hollow channels of the THF, surface tension measurements are possible by simply tracking the Fresnel reflection at the distal end of the THF. Our results show that the characteristic times involved in the bubble formation process, from where the surface tension of the liquids under test is retrieved, can be measured from the train of pulses generated by the continuous formation and detachment of bubbles.

Intelligent Image De-Blurring for Imaging Flow Cytometry.

By virtue of the combined merits of optical microscopy and flow cytometry, imaging flow cytometry is a powerful tool for rapid, high-content analysis of single cells in large heterogeneous populations. However, its efficiency (defined by the ratio of the number of clearly imaged cells to the total cell population) is not high (typically 50-80%), due to out-of-focus image blurring caused by imperfect fluidic focusing of cells, a common drawback that not only reduces the number of cell images useable for high-content analysis but also increases the probability of false events and missed rare cells. To address this challenge and expand the efficacy of imaging flow cytometry, here, we propose and demonstrate intelligent deblurring of out-of-focus cell images in imaging flow cytometry. Specifically, by using our machine learning algorithms, we show an 11% increase in variance and a 95% increase in first-order gradient summation of cell images taken with an optofluidic time-stretch microscope. Without strict hardware requirements, our intelligent de-blurring method provides a promising solution to the out-of-focus blurring problem of imaging flow cytometers and holds promise for significantly improving their performance. © 2019 International Society for Advancement of Cytometry.

Optofluidic time-stretch quantitative phase microscopy.

Innovations in optical microscopy have opened new windows onto scientific research, industrial quality control, and medical practice over the last few decades. One of such innovations is optofluidic time-stretch quantitative phase microscopy - an emerging method for high-throughput quantitative phase imaging that builds on the interference between temporally stretched signal and reference pulses by using dispersive properties of light in both spatial and temporal domains in an interferometric configuration on a microfluidic platform. It achieves the continuous acquisition of both intensity and phase images with a high throughput of more than 10,000 particles or cells per second by overcoming speed limitations that exist in conventional quantitative phase imaging methods. Applications enabled by such capabilities are versatile and include characterization of cancer cells and microalgal cultures. In this paper, we review the principles and applications of optofluidic time-stretch quantitative phase microscopy and discuss its future perspective.

Robust Smartphone Assisted Biosensing Based on Asymmetric Nanofluidic Grating Interferometry.

Point-of-care systems enable fast therapy decisions on site without the need of any healthcare infrastructure. In addition to the sensitive detection, stable measurement by inexperienced persons outside of laboratory facilities is indispensable. A particular challenge in field applications is to reduce interference from environmental factors, such as temperature, to acceptable levels without sacrificing simplicity. Here, we present a smartphone-based point-of-care sensor. The method uses an optofluidic grating composed of alternating detection and reference channels arranged as a reflective phase grating. Biomolecules adsorbing to the detection channel alter the optical path length, while the parallel reference channels enable a direct common mode rejection within a single measurement. The optical setup is integrated in a compact design of a mobile readout device and the usability is ensured by a smartphone application. Our results show that different ambient temperatures do not have any influence on the signal. In a proof-of concept experiment we measured the accumulation of specific molecules in functionalized detection channels in real-time and without the need of any labeling. Therefore, the channel walls have been modified with biotin as capture molecules and the specific binding of streptavidin was detected. A mobile, reliable and robust point-of-care device has been realized by combining an inherently differential measurement concept with a smartphone-based, mobile readout device.

Miniaturized, Battery-Free Optofluidic Systems with Potential for Wireless Pharmacology and Optogenetics.

Combination of optogenetics and pharmacology represents a unique approach to dissect neural circuitry with high specificity and versatility. However, conventional tools available to perform these experiments, such as optical fibers and metal cannula, are limited due to their tethered operation and lack of biomechanical compatibility. To address these issues, a miniaturized, battery-free, soft optofluidic system that can provide wireless drug delivery and optical stimulation for spatiotemporal control of the targeted neural circuit in freely behaving animals is reported. The device integrates microscale inorganic light-emitting diodes and microfluidic drug delivery systems with a tiny stretchable multichannel radiofrequency antenna, which not only eliminates the need for bulky batteries but also offers fully wireless, independent control of light and fluid delivery. This design enables a miniature (125 mm3 ), lightweight (220 mg), soft, and flexible platform, thus facilitating seamless implantation and operation in the body without causing disturbance of naturalistic behavior. The proof-of-principle experiments and analytical studies validate the feasibility and reliability of the fully implantable optofluidic systems for use in freely moving animals, demonstrating its potential for wireless in vivo pharmacology and optogenetics.

Continuous and Real-Time Detection of Drinking-Water Pathogens with a Low-Cost Fluorescent Optofluidic Sensor.

Growing access to tap water and consequent expansion of water distribution systems has created numerous challenges to maintaining water quality between the treatment node and final consumer. Despite all efforts to develop sustainable monitoring systems, there is still a lack of low cost, continuous and real time devices that demonstrate potential for large-scale implementation in wide water distribution networks. The following work presents a study of a low-cost, optofluidic sensor, based on Trypthopan Intrinsic Fluorescence. The fluorospectrometry analysis performed (before sensor development) supports the existence of a measurable fluorescence output signal originating from the tryptophan contained within pathogenic bacteria. The sensor was mounted using a rapid prototyping technique (3D printing), and the integrated optical system was achieved with low-cost optical components. The sensor performance was evaluated with spiked laboratory samples containing E. coli and Legionella, in both continuous and non-continuous flow situations. Results have shown a linear relationship between the signal measured and pathogen concentration, with limits of detection at 1.4 × 10³ CFU/mL. The time delay between contamination and detection of the bacteria was practically null. Therefore, this study supports the potential application of tryptophan for monitoring drinking water against water pathogens.

Photoresistance switching of plasmonic nanopores.

Fast and reversible modulation of ion flow through nanosized apertures is important for many nanofluidic applications, including sensing and separation systems. Here, we present the first demonstration of a reversible plasmon-controlled nanofluidic valve. We show that plasmonic nanopores (solid-state nanopores integrated with metal nanocavities) can be used as a fluidic switch upon optical excitation. We systematically investigate the effects of laser illumination of single plasmonic nanopores and experimentally demonstrate photoresistance switching where fluidic transport and ion flow are switched on or off. This is manifested as a large (∼ 1-2 orders of magnitude) increase in the ionic nanopore resistance and an accompanying current rectification upon illumination at high laser powers (tens of milliwatts). At lower laser powers, the resistance decreases monotonically with increasing power, followed by an abrupt transition to high resistances at a certain threshold power. A similar rapid transition, although at a lower threshold power, is observed when the power is instead swept from high to low power. This hysteretic behavior is found to be dependent on the rate of the power sweep. The photoresistance switching effect is attributed to plasmon-induced formation and growth of nanobubbles that reversibly block the ionic current through the nanopore from one side of the membrane. This explanation is corroborated by finite-element simulations of a nanobubble in the nanopore that show the switching and the rectification.

Dual characterization of biological cells by optofluidic microscope and resistive pulse sensor.

Label-free detection technique has emerged as a powerful platform for biomedical applications since it can avoid laborious multi-step sample preparation. In this paper, we demonstrate a dual analysis of biological cells using a single microfluidic system combining optofluidic microscopy and resistive pulse sensing. Both red blood cells (RBCs) and circulating tumor cells (CTCs) have been used to validate the concept of dual analysis and also to test the performance of the microfluidic device. The cell characterization by resistive pulse sensing is in good agreement with the analysis by optofluidic microscopy, further verified by the commercial Beckman-Coulter® FC500 flow cytometry. The present system has attractive merits such as simple fabrication, easy integration, high portability, and low cost. This study has great potentials for the development of innovative on-chip flow cytometry with concurrent imaging sensing and resistive sensing.

Fully Active Delivery of Nanodrugs In Vivo via Remote Optical Manipulation.

The active delivery of nanodrugs has been a bottleneck problem in nanomedicine. While modification of nanodrugs with targeting agents can enhance their retention at the lesion location, the transportation of nanodrugs in the circulation system is still a passive process. The navigation of nanodrugs with external forces such as magnetic field has been shown to be effective for active delivery, but the existing techniques are limited to specific materials like magnetic nanoparticles. In this study, an alternative actuation method is proposed based on optical manipulation for remote navigation of nanodrugs in vivo, which is compatible with most of the common drug carriers and exhibits significantly higher manipulation precision. By the programmable scanning of the laser beam, the motion trajectory and velocity of the nanodrugs can be precisely controlled in real time, making it possible for intelligent drug delivery, such as inverse-flow transportation, selective entry into specific vascular branch, and dynamic circumvention across obstacles. In addition, the controlled mass delivery of nanodrugs can be realized through indirect actuation by the microflow field. The developed optical manipulation method provides a new solution for the active delivery of nanodrugs, with promising potential for the treatment of blood diseases such as leukemia and thrombosis.

Determination of Enantiomeric Excess by Optofluidic Microlaser near Exceptional Point.

Enantiomeric excess (ee) is an essential indicator of chiral drug purification in the pharmaceutical industry. However, to date the ee determination of unknown concentration enantiomers generally involves two separate techniques for chirality and concentration measurement. Here, a whispering-gallery mode (WGM) based optofluidic microlaser near exceptional point to achieve the ee determination under unknown concentration with a single technique is proposed. Exceptional point induces the unidirectional WGM lasing, providing the optofluidic microlaser with the novel capability to measure chirality by polarization, in addition to wavelength-based concentration detection. The dual-parameters detection of optofluidic microlaser empowers it to achieve ee determination of various unknown enantiomers without additional concentration measurements, a feat that is challenging to accomplish with other methods. Featuring the sensitivity enhancement and miniature structure of the WGM sensors, the obtained chiroptical response of the present approach is ≈30-fold higher than that of the conventional optical rotation-based polarimeter, and the reagent consumption is reduced by three orders of magnitude.

Rapid, sensitive, and non-destructive on-site quantitative detection of nanoplastics in aquatic environments using laser-backscattered fiber-embedded optofluidic chip.

A definitive link between the micro- and nano-plastics (NPLs) and human health has been firmly established, emphasizing the higher risks posed by NPLs. The urgent need for a rapid, non-destructive, and reliable method to quantify NPLs remains unmet with current detection techniques. To address this gap, a novel laser-backscattered fiber-embedded optofluidic chip (LFOC) was constructed for the rapid, sensitive, and non-destructive on-site quantitation of NPLs based on 180º laser-backscattered mechanism. Our theoretical and experimental findings reveal that the 180º laser-backscattered intensities of NPLs were directly proportional to their mass and particle number concentration. Using the LFOC, we have successfully detected polystyrene (PS) NPLSs of varying sizes, with a minimum detection limit of 0.23 µg/mL (equivalent to 5.23 ×107 particles/mL). Moreover, PS NPLs of different sizes can be readily differentiated through a simple membrane-filtering method. The LFOC also demonstrates high sensitivity in detecting other NPLs, such as polyethylene, polyethylene terephthalate, polypropylene, and polymethylmethacrylate. To validate its practical application, the LFOC was used to detect PS NPLs in various aquatic environments, exhibiting excellent accuracy, reproducibility, and reliability. The LFOC provides a simple, versatile, and efficient tool for direct, on-site, quantitative detection of NPLs in aquatic environments.