Microring resonator-assisted Fourier transform spectrometer with enhanced resolution and large bandwidth in single chip solution.

Single chip integrated spectrometers are critical to bring chemical and biological sensing, spectroscopy, and spectral imaging into robust, compact and cost-effective devices. Existing on-chip spectrometer approaches fail to realize both high resolution and broad band. Here we demonstrate a microring resonator-assisted Fourier-transform (RAFT) spectrometer, which is realized using a tunable Mach-Zehnder interferometer (MZI) cascaded with a tunable microring resonator (MRR) to enhance the resolution, integrated with a photodetector onto a single chip. The MRR boosts the resolution to 0.47 nm, far beyond the Rayleigh criterion of the tunable MZI-based Fourier-transform spectrometer. A single channel achieves large bandwidth of ~ 90 nm with low power consumption (35 mW for MRR and 1.8 W for MZI) at the expense of degraded signal-to-noise ratio due to time-multiplexing. Integrating a RAFT element array is envisaged to dramatically extend the bandwidth for spectral analytical applications such as chemical and biological sensing, spectroscopy, image spectrometry, etc.

Author Correction: Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

The original version of this Article omitted the author Kuan Wang, who is from the 'College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan' and 'Nanyang Environment & Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore.'Also, the author S.H. Lim was incorrectly given as L.S. Hoi and A. Larsson was incorrectly given as A. Larson.The "Author contributions" was amended to reflect the authorship changes. It previously read 'Y.Z.S., C.-W.Q., and A.Q.L. jointly conceived the idea. Y.Z.S., S.X., Y.Z., J.B.Z., W.S., J.H.W., T.N.C., Z.C.Y., Y.L.H., B.L., P.H.Y., D.P.T., and C.-W.Q. performed the numerical simulations and theoretical analysis. Y.Z.S., S.X., and L.K.C. did the fabrication and experiments of particle hopping, biomolecule binding and flow cytometry. A.L. and L.S.H. did the SPR experiments. S.X., Y.Z.S., Y.Z., C.-W.Q., Y.-Y.C., L.K.C., T.H.Z., and A.Q.L. prepared the manuscript. S.X., Y.Z., C.-W.Q., and A.Q.L. supervised and coordinated all the work. All authors commented on the manuscript.' The correct version states 'B.L., K. W., P.H.Y.' instead of 'B.L., P.H.Y.' and 'S.H.L.' in place of 'L.S.H.'This has been corrected in both the PDF and HTML versions of the Article.

Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.

High-resolution and multi-range particle separation by microscopic vibration in an optofluidic chip.

An optofluidic chip is demonstrated in experiments for high-resolution and multi-range particle separation through the optically-induced microscopic vibration effect, where nanoparticles are trapped in loosely overdamped optical potential wells created with combined optical and fluidic constraints. It is the first demonstration of separating single nanoparticles with diameters ranging from 60 to 100 nm with a resolution of 10 nm. Nanoparticles vibrate with an amplitude of 3-7 µm in the loosely overdamped potential wells in the microchannel. The proposed optofluidic device is capable of high-resolution particle separation at both nanoscale and microscale without reconfiguring the device. The separation of bacteria from other larger cells is accomplished using the same chip and operation conditions. The unique trapping mechanism and the superb performance in high-resolution and multi-range particle separation of the proposed optofluidic chip promise great potential for a diverse range of biomedical applications.

Correction: Optofluidic lens with low spherical and low field curvature aberrations.

Correction for 'Optofluidic lens with low spherical and low field curvature aberrations' by H. T. Zhao et al., Lab Chip, 2016, 16, 1617-1624.

Optofluidic lens with low spherical and low field curvature aberrations.

This paper reports an optofluidic lens with low spherical and low field curvature aberrations through the desired refractive index profile by precisely controlling the mixing between ethylene glycol and deionized water in an optofluidic chip. The experimental results demonstrate that the spherical aberration is reduced to 19.5 µm and the full width at half maximum of the focal point is 7.8 µm with a wide divergence angle of 35 degrees. In addition, the optofluidic lens can focus light at different off-axis positions on the focal plane with Δx' < 6.8 µm and at opposite transverse positions with |Δy - Δy'| < 5.7 µm. This is the first demonstration of a special optofluidic lens that significantly reduces both the spherical and field curvature aberrations, which enhances the focusing power and facilitates multiple light source illumination using a single lens. It is anticipated to have high potential for applications such as on-chip light manipulation, sample illumination and multiplexed detection.

Cell refractive index for cell biology and disease diagnosis: past, present and future.

Cell refractive index is a key biophysical parameter, which has been extensively studied. It is correlated with other cell biophysical properties including mechanical, electrical and optical properties, and not only represents the intracellular mass and concentration of a cell, but also provides important insight for various biological models. Measurement techniques developed earlier only measure the effective refractive index of a cell or a cell suspension, providing only limited information on cell refractive index and hence hindering its in-depth analysis and correlation. Recently, the emergence of microfluidic, photonic and imaging technologies has enabled the manipulation of a single cell and the 3D refractive index of a single cell down to sub-micron resolution, providing powerful tools to study cells based on refractive index. In this review, we provide an overview of cell refractive index models and measurement techniques including microfluidic chip-based techniques for the last 50 years, present the applications and significance of cell refractive index in cell biology, hematology, and pathology, and discuss future research trends in the field, including 3D imaging methods, integration with microfluidics and potential applications in new and breakthrough research areas.

Water's tensile strength measured using an optofluidic chip.

In this paper, for the first time, the tensile strength of water is directly measured using an optofluidic chip based on the displacement of air-water interface deformation with homogeneous nucleation. When water in a microchannel is stretched dynamically via laser-induced shock reflection at the air-water interface, the shock pressures are determined by measuring the displacements of the deformed interface. Observation of the vapor bubbles is used as a probe to identify the cavitation threshold with a critical distance, and the tensile strength of water at 20 °C is measured to be -33.3 ± 2.8 MPa. This method can be extended to investigate the tensile strength of other soft materials such as glycerol, which is measured to be -59.8 ± 10.7 MPa at 20 °C.

Droplet generation via a single bubble transformation in a nanofluidic channel.

Here we report the first demonstration on droplet generation from the transformation of a single bubble in a nanofluidic channel by a laser-induced jet. A viscous two-dimensional Rayleigh-Plesset-type model is derived to describe the bubble dynamics in the nanofluidic channel, which accounts for the effect of shear stresses from the channel wall. The droplet generation (number and volume) is investigated experimentally by controlling the jet velocity via laser energy and distance. This study expands the understanding of jetting in the nanofluidic channel and demonstrates a novel method for femtoliter-volume single or multiple droplet formation. It is envisioned that this work will open new doors in on-demand generation of nanodroplets.

An optofluidic imaging system to measure the biophysical signature of single waterborne bacteria.

In this paper, for the first time, an on-chip optofluidic imaging system is innovated to measure the biophysical signatures of single waterborne bacteria, including both their refractive indices and morphologies (size and shape), based on immersion refractometry. The key features of the proposed optofluidic imaging platform include (1) multiple sites for single-bacterium trapping, which enable parallel measurements to achieve higher throughput, and (2) a chaotic micromixer, which enables efficient refractive index variation of the surrounding medium. In the experiments, the distinctive refractive index of Echerichia coli, Shigella flexneri and Vibrio cholera are measured with a high precision of 5 × 10(-3) RIU. The developed optofluidic imaging system has high potential not only for building up a database of biophysical signatures of waterborne bacteria, but also for developing single-bacterium detection in treated water that is in real-time, label-free and low cost.

Droplet optofluidic imaging for λ-bacteriophage detection via co-culture with host cell Escherichia coli.

Bacteriophages are considered as attractive indicators for determining drinking water quality since its concentration is strongly correlated with virus concentrations in water samples. Previously, bacteriophage detection was based on a plague assay that required a complicated labelling technique and a time-consuming culture assay. Here, for the first time, a label-free bacteriophage detection is reported by using droplet optofluidic imaging, which uses host-cell-containing microdroplets as reaction carriers for bacteriophage infection due to a higher contact ratio. The optofluidic imaging is based on the effective refractive index changes in the microdroplet correlated with the growth rate of the infected host cells, which is highly sensitive, i.e. can detect one E. coli cell. The droplet optofluidic system is not only used in drinking water quality monitoring, but also has high potential applications for pathogenic bacteria detection in clinical diagnosis and food industry.

Study of endothelial cell apoptosis using fluorescence resonance energy transfer (FRET) biosensor cell line with hemodynamic microfluidic chip system.

To better understand how hyperglycemia induces endothelial cell dysfunction under the diabetic conditions, a hemodynamic microfluidic chip system was developed. The system combines a caspase-3-based fluorescence resonance energy transfer (FRET) biosensor cell line which can detect endothelial cell apoptosis in real-time, post-treatment effect and with a limited cell sample, by using a microfluidic chip which can mimic the physiological pulsatile flow profile in the blood vessel. The caspase-3-based FRET biosensor endothelial cell line (HUVEC-C3) can produce a FRET-based sensor protein capable of probing caspase-3 activation. When the endothelial cells undergo apoptosis, the color of the sensor cells changes from green to blue, thus sensing apoptosis. A double-labeling fluorescent technique (yo pro-1 and propidium iodide) was used to validate the findings revealed by the FRET-based caspase sensor. The results show high rates of apoptosis and necrosis of endothelial cells when high glucose concentration was applied in our hemodynamic microfluidic chip combined with an exhaustive pulsatile flow profile. The two apoptosis detection techniques (fluorescent method and FRET biosensor) are comparable; but FRET biosensor offers more advantages such as real-time observation and a convenient operating process to generate more accurate and reliable data. Furthermore, the activation of the FRET biosensor also confirms the endothelial cell apoptosis induced by the abnormal pulsatile shear stress and high glucose concentration is through caspase-3 pathway. A 12% apoptotic rate (nearly a 4-fold increase compared to the static condition) was observed when the endothelial cells were exposed to a high glucose concentration of 20 mM under 2 h exhaustive pulsatile shear stress of 30 dyne cm(-2) and followed with another 10 h normal pulsatile shear stress of 15 dyne cm(-2). Therefore, the most important finding of this study is to develop a novel endothelial cell apoptosis detection method, which combines the microfluidic chip system and FRET biosensor. This finding may provide new insight into how glucose causes endothelial cell dysfunction, which is the major cause of diabetes-derived complications.

Transformation optofluidics for large-angle light bending and tuning.

Transformation optics is a new art of light bending by designing materials with spatially variable parameters for developing wave-manipulation devices. Here, we introduce a transformation optofluidic Y-branch splitter with large-angle bending and tuning based on the design of a spatially variable index. Differing from traditional splitters, the optofluidic splitter is achieved in an inhomogeneous medium by coordinate transformation. The designed bidirectional gradient index (GRIN) distribution can be achieved practically by the convection-diffusion process of liquid flowing streams. The transformation optofluidic splitter can achieve a much larger split angle with little bend loss than the traditional ones. In the experiments, a large tunable split angle up to 30° is achieved by tuning the flow rates, allowing optical signals to be freely transferred to different channels. Besides the symmetrical branch splitting, asymmetrical Y-branch splitting with approximately equal power splitting is also demonstrated by changing the composition of the liquids. The optofluidic splitter has high potential applications in biological, chemical and biomedical solution measurement and detection.

Australian immunisation registers: established foundations and opportunities for improvement.

The National Immunisation Program Schedule in Australia is formulated and funded nationally under the population-wide Medicare system. The policy is implemented by the eight state and territory jurisdictions. The national immunisation registers consist of the Australian Childhood Immunisation Register (ACIR), and, more recently, the National Human Papillomavirus (HPV) Vaccination Program Register. Moreover, a variety of jurisdiction-based registers and primary care practice software systems exist, which interact with the national registers. General practitioners can obtain reports listing patients under seven years attending their practice and recorded as 'not fully immunised', and immunisation coverage rates for their practice linked to government incentives through Medicare. A 2011 report documents national coverage of 91.8% fully immunised at 12 months, and 92.6% at 24 months. The HPV register provides information on vaccination coverage with the potential to link with a register of cervical cancer screening results. Limitations of current national register include inability to easily access immunisation histories beyond seven years of age, and issues of underreporting and timeliness, which impact significantly the immunisation coverage estimates. The linkage of these registers with healthcare outcome data will further enhance public health outcomes by enabling rapid, population-level vaccine safety and effectiveness investigations in a nation with a track record as an 'early adopter' of new childhood vaccines.

Optofluidic waveguide as a transformation optics device for lightwave bending and manipulation.

Transformation optics represents a new paradigm for designing light-manipulating devices, such as cloaks and field concentrators, through the engineering of electromagnetic space using materials with spatially variable parameters. Here we analyse liquid flowing in an optofluidic waveguide as a new type of controllable transformation optics medium. We show that a laminar liquid flow in an optofluidic channel exhibits spatially variable dielectric properties that support novel wave-focussing and interference phenomena, which are distinctively different from the discrete diffraction observed in solid waveguide arrays. Our work provides new insight into the unique optical properties of optofluidic waveguides and their potential applications.

A tunable 3D optofluidic waveguide dye laser via two centrifugal Dean flow streams.

This paper presents a tunable optofluidic waveguide dye laser utilizing two centrifugal Dean flows. The centrifugal Dean flow increases the light confinement of the dye laser by shaping a three-dimensional (3D) liquid waveguide from curved microchannels. The active medium with the laser dye is dissolved in the liquid core and pumped with an external pump laser to produce stimulated emission. The laser's Fabry-Pérot microcavity is formed with a pair of aligned gold-coated fiber facets to amplify the fluorescent emission. The advantage of the 3D optofluidic waveguide dye laser is its higher efficiency, thus to obtain lasing at a reduced threshold (60%) with higher output energy. The demonstrated slope efficiency is at least 3-fold higher than its traditional two-dimensional equivalent. In addition, the laser output energy can be varied on demand by tuning the flow rates of the two flows. This technique provides a versatile platform for high potential applications microfluidic biosensor and bioanalysis.

Production of reactive oxygen species in endothelial cells under different pulsatile shear stresses and glucose concentrations.

A hemodynamic Lab-on-a-chip system was developed in this study. This system has two unique features: (1) it consists of a microfluidic network with an array of endothelial cell seeding sites for testing them under multiple conditions, and (2) the flow rate and the frequency of the culture medium in the microchannel are controlled by a pulsation free pump to mimic the flow profile of the blood in the blood vessel under different physiological conditions. The investigated physiological conditions were: (1) the resting condition in a normal shear stress of 15 dyne cm(-2) with a normal heart rate of 70 bpm, (2) an exhaustive exercise condition with a high shear stress of 30 dyne cm(-2) and a fast heart rate of 140 bpm, and (3) a constant high shear stress of 30 dyne cm(-2). Two chemical conditions were investigated (10 mM and 20 mM glucose) to mimic hyperglycemic conditions in diabetes patients. The effects of various shear stresses either alone or in combination with different glucose concentrations on endothelial cells were examined using the developed hemodynamic Lab-on-a-chip system by assessing two parameters. One is the intracellular level of reactive oxygen species (ROS) determined by a fluorescent probe, H(2)DCFDA. Another is the mitochondrial morphology revealed with a fluorescent dye, MitoTracker Green FM. The results showed that ROS level was elevated nearly 4-fold after 60 min of exhaustive exercise. We found that the pulsatile nature of the fluid was the determination factor for causing ROS generation in the cells as almost no increase of ROS was detected in the constant shear stress condition. Similarly, much higher level of ROS was detected when 10 mM glucose was applied to the cells under normal or high pulsatile shear stresses compared with under a static condition. These results suggest that it is necessary to use pulsatile shear stress to represent the physiological conditions of the blood flow, and demonstrate the advantage of utilizing this newly developed hemodynamic Lab-on-a-chip system over the conventional non-pulsatile system in the future shear stress related studies.

An optofluidic prism tuned by two laminar flows.

This paper presents a tunable optofluidic prism based on the configuration of two laminar flow streams with different refractive indices in a triangular chamber. The chambers with 70° and 90° apex angles are designed based on simulation results, which provide the optimum working range and avoid recirculating flows in the chambers. In addition, a hydrodynamic model has been developed to predict the tuning of the prisms by the variation in the flow rates. Prisms with different refractive indices are realized using benzyl alcohol and deionized (DI) water as the inner liquids, respectively. The mixture of ethylene glycol and DI water with an effective refractive index matched to that of the microchannel is used as the outer liquid. The apex angle of the prism is tuned from 75° to 135° by adjusting the ratio of the two flow rates. Subsequently, the deviation angle of the output light beam is tuned from -13.5° to 22°. One of the new features of this optofluidic prism is its capability to transform from a symmetric to an asymmetric prism with the assistance of a third flow. Two optical behaviours have been performed using the optofluidic prism. First, parallel light beam scanning is achieved with a constant deviation angle of 10° and a tuning range of 60 µm using the asymmetric prism. The detected output light intensity is increased by 65.7%. Second, light dispersion is experimentally demonstrated using 488-nm and 633-nm laser beams. The two laser beams become distinguishable with a deviation angle difference of 2.5° when the apex angle of the prism reaches 116°.

An optofluidic volume refractometer using Fabry-Pérot resonator with tunable liquid microlenses.

This letter reports the development of an optofluidic Fabry-Pérot (FP) resonator, which consists of a microcavity and a pair of liquid microlenses. The microcavity forms part of the microchannel to facilitate sample injection. The liquid microlenses are used for efficient light coupling from the optical fiber to the microcavity. The liquid microlens collimates the diverging light from the optical fiber into the FP cavity, which provides real-time tuning to obtain the highest possible finesse up to 18.79. In volume refractive index measurement, a sensitivity of 960 nm per refractive index unit (RIU) and a detection range of 0.043 RIU are achieved.

Microfluidic droplet grating for reconfigurable optical diffraction.

This Letter presents a reconfigurable optical diffraction grating using multiphase droplets on a microfluidic chip. The uniform and evenly spaced circular droplets are generated by continuously dispersing two immiscible liquids into a T junction to produce plugs, which are then transformed into a circular shape at a sudden expansion of the microchannel. In experiments, the droplet grating shows a detection limit of ~6.3x10(-5) when used as an opto fl uidic refractometer and produces different colors as a color filter. Such a grating has the advantages of high stability and wide tunability in droplet size, grating period, and refractive index, making it promising for biochemical and biomaterial applications.