On-Demand Coalescence of Ferromagnetic Droplets in Microchannels Using an Oscillating Magnetic Field.

Droplet-based microfluidics exhibit remarkable potential in achieving high-throughput chemical reactions with minimal reagent consumption. However, a pivotal challenge lies in the selective coalescence of droplets for precise process control, particularly when dealing with droplets of varying amounts and volumes, which are difficult to trap and coalesce due to their tiny dimensions and incessant movement. Hence, we proposed a method for on-demand coalescence of ferromagnetic droplets using an oscillating magnetic field. Experimental results show that the ferromagnetic droplets can be trapped in different positions in the microchannels according to the applied magnetic field intensity. A high-intensity pulsed amplitude of the magnetic field enables the migration of trapped droplets toward the same position, facilitating their mutual contact and interaction. By programmable modulation of the oscillating magnetic field, a controllable reciprocation of droplets in microchannels was successfully realized, which enabled us to dynamically capture, coalesce, and release two or more (≥3) droplets on demand. The integrated ferromagnetic droplet-based microfluidic platform allows contact-free, easily monitored, and on-demand coalescence of ferromagnetic droplets in microchannels, which holds promise for a wide range of applications, such as microfluidic-based drug synthesis, biosensing, reaction kinetics, and paracrine signaling, particularly.

On-Chip Photoacoustics-Activated Cell Sorting (PA-ACS) for Label-Free and High-Throughput Detection and Screening of Microalgal Cells.

Microalgae play a crucial role in global carbon cycling as they convert carbon dioxide into various valuable macromolecules. Among them, Haematococcus pluvialis (H. pluvialis) is the richest natural source of astaxanthin (AXT), which is a valuable antioxidant, anti-inflammatory, and antiapoptosis agent. These benefits make AXT highly commercially valuable in pharmaceuticals, cosmetics, and nutritional industries. However, intrinsic genetic characteristics and extrinsic cultivation conditions influence biomass gains, leading to low productivity and extraction as the main techno-economic bottlenecks in this industry. Thus, detecting AXT in H. pluvialis is essential to determine the influence of multiple parameters on biocompound accumulation, enabling optimization of cultivation and enrichment of AXT-rich H. pluvialis cells. This work developed an opto-acousto-fluidic microplatform for detection, analysis, and sorting of microalgae. Via label-free monitoring and extraction of sample-induced ultrasonic signals, a photoacoustic microscopic system was proposed to provide a full-field visualization of AXT's content and distribution inside H. pluvialis cells. When employed as on-chip image-based flow cytometry, our microplatform can also offer high-throughput measurements of intracellular AXT in real time, which demonstrates similar results to conventional spectrophotometry methods and further reveals the heterogeneity of AXT content at the single-cell level. In addition, a solenoid valve-pump dual-mode cell sorter was integrated for effective sorting of cells with a maximum working frequency of 0.77 Hz, reducing the fluid response time by 50% in rising and 40-fold in recovery. The H. pluvialis cells which have more AXT accumulation (>30 µm in diameter) were 4.38-fold enriched with almost no dead empty and small green cells. According to the results, automated and reliable photoacoustics-activated cell sorting (PA-ACS) can screen AXT-rich cells and remove impurities at the terminal stage of cultivation, thereby increasing the effectiveness and purity of AXT extraction. The proposed system can be further adopted to enrich strains and mutants for the production of biofuels or other rare organic substances such as ß-carotene and lutein.

Dispersive phase microscopy incorporated with droplet-based microfluidics for biofactory-on-a-chip.

Biomolecular imaging of intracellular structures of a single cell and subsequent screening of the cells are of high demand in metabolic engineering to develop strains with the desired phenotype. However, the capability of current methods is limited to population-scale identification of cell phenotyping. To address this challenge, we propose to utilize dispersive phase microscopy incorporated with a droplet-based microfluidic system that combines droplet volume-on-demand generation, biomolecular imaging, and droplet-on-demand sorting, to achieve high-throughput screening of cells with an identified phenotype. Particularly, cells are encapsulated in homogeneous environments with microfluidic droplet formation, and the biomolecule-induced dispersive phase can be investigated to indicate the biomass of a specific metabolite in a single cell. The retrieved biomass information consequently guides the on-chip droplet sorting unit to screen cells with the desired phenotype. To demonstrate the proof of concept, we showcase the method by promoting the evolution of the Haematococcus lacustris strain toward a high production of natural antioxidant astaxanthin. The validation of the proposed system with on-chip single-cell imaging and droplet manipulation functionalities reveals the high-throughput single-cell phenotyping and selection potential that applies to many other biofactory scenarios, such as biofuel production, critical quality attribute control in cell therapy, etc.

Growth Characteristic Analysis of Haematococcus pluvialis in a Microfluidic Chip Using Digital in-Line Holographic Flow Cytometry.

In order to obtain high yield of astaxanthin, a high-value compound with ultrastrong antioxidant capacity, it is necessary to identify the growth characteristics (biomass, morphology, and size) of Haematococcus pluvialis. The current detection methods have the disadvantages of labor-consuming operation or complicated measurement system. It is an urgent need to explore a simple and cost-effective method for the detection of H. pluvialis with large size distribution during its growth period. In this work, a digital in-line holographic flow cytometry using a linear array sensor is proposed to measure the growth characteristics of H. pluvialis in a two-dimensional (2-D) hydrodynamic focusing microfluidic chip. Based on the modified angular spectrum method, the distorting holograms caused by the asynchrony of sample flow velocity and acquisition speed of the linear array sensor were rectified and reconstructed. In addition, the depth-of-focus of the imaging system were digitally extended to cover the entire depth of the microfluidic channel for optimized imaging quality. We have utilized the proposed method to statistically investigate the biomass, morphology and size of H. pluvialis under different culture conditions and growth durations.

The Fusion of Microfluidics and Optics for On-Chip Detection and Characterization of Microalgae.

It has been demonstrated that microalgae play an important role in the food, agriculture and medicine industries. Additionally, the identification and counting of the microalgae are also a critical step in evaluating water quality, and some lipid-rich microalgae species even have the potential to be an alternative to fossil fuels. However, current technologies for the detection and analysis of microalgae are costly, labor-intensive, time-consuming and throughput limited. In the past few years, microfluidic chips integrating optical components have emerged as powerful tools that can be used for the analysis of microalgae with high specificity, sensitivity and throughput. In this paper, we review recent optofluidic lab-on-chip systems and techniques used for microalgal detection and characterization. We introduce three optofluidic technologies that are based on fluorescence, Raman spectroscopy and imaging-based flow cytometry, each of which can achieve the determination of cell viability, lipid content, metabolic heterogeneity and counting. We analyze and summarize the merits and drawbacks of these micro-systems and conclude the direction of the future development of the optofluidic platforms applied in microalgal research.

Acoustic Standing Wave Aided Multiparametric Photoacoustic Imaging Flow Cytometry.

Photoacoustic imaging reveals great potential for the study of individual cells due to the rich imaging contrast for both label-free and labeled cells. However, previously reported photoacoustic imaging flow cytometry configuration suffers from inadequate imaging quality and challenge to distinguish multiple cells. In order to solve such issues, we propose a novel acoustic standing wave aided multiparametric photoacoustic imaging flow cytometry (MPAFC) system. The acoustic standing wave is introduced to improve the imaging quality and speed. Multispectral illumination along with cell geometry, photoacoustic amplitude, and acoustic frequency spectrum enables the proposed system to precisely identify multiple types of cells with one scanning. On the basis of the identification, elimination of melanoma cells, and targeted labeled glioma cells have been performed with an elimination efficiency of >95%. Additionally, the MPAFC system is able to image and capture melanoma cells at a lowest concentration of 100 cells mL-1 in pure blood. Current results suggest that the proposed MPAFC may provide a precise and efficient tool for cell detection, manipulation, and elimination in both fundamental and clinical studies.

On-Chip Multicolor Photoacoustic Imaging Flow Cytometry.

On-chip imaging flow cytometry has been widely used in cancer biology, immunology, microbiology, and drug discovery. Pure optical imaging combined with flow cytometry to derive chemical, structural, and morphological features of cells provides systematic insights into biological processes. However, due to the high concentration and strong optical attenuation of red blood cells, preprocessing is necessary for optical flow cytometry while dealing with whole blood. In this study, we develop an on-chip photoacoustic imaging flow cytometry (PAIFC), which combines multicolor high-speed photoacoustic microscopy and microfluidics for cell imaging. The device employs a micro-optical scanner to achieve a miniaturized outer size of 30 × 17 × 24 mm3 and ultrafast cross-sectional imaging at a frame rate of 1758 Hz and provides lateral and axial resolutions of 2.2 and 33 µm, respectively. Using a multicolor strategy, PAIFC is able to differentiate cells labeled by external contrast agents, detect melanoma cells with an endogenous contrast in whole blood, and image melanoma cells in blood samples from tumor-bearing mice. The results suggest that PAIFC has sufficient sensitivity and specificity for future cell-on-chip applications.

Three-dimensional visualization and analysis of flowing droplets in microchannels using real-time quantitative phase microscopy.

Recent years have witnessed the development of droplet-based microfluidics as a useful and effective tool for high-throughput analysis in biological, chemical and environmental sciences. Despite the flourishing development of droplet manipulation techniques, only a few methods allow for label-free and quantitative inspection of flowing droplets in microchannels in real-time and in three dimensions (3-D). In this work, we propose and demonstrate the application of a real-time quantitative phase microscopy (RT-QPM) technique for 3-D visualization of droplets, and also for full-field and label-free measurement of analyte concentration distribution in the droplets. The phase imaging system consists of a linear-CCD-based holographic microscopy configuration and an optofluidic phase-shifting element, which can be used for retrieving quantitative phase maps of flowing objects in the microchannels with a temporal resolution only limited to the frame rate of the CCD camera. To demonstrate the capabilities of the proposed imaging technique, we have experimentally validated the 3-D image reconstruction of the droplets generated in squeezing and dripping regimes and quantitatively investigated the volumetric and morphological variation of droplets as well as droplet parameters related to the depth direction under different flow conditions. We also demonstrated the feasibility of using this technique, as a refractive index sensor, for in-line quantitative measurement of carbamide analyte concentration within the flowing droplets.

Study on the dual-Fano resonance generation and its potential for self-calibrated sensing.

Sensors based on Fano resonance (FR) have become a promising platform for various biological and chemical applications. However, most investigations on FR are limited to the generation of individual resonance. In this paper, based on the coupling between surface plasmon polariton (SPP) and two photonic waveguide modes, a dual-FR system is designed and analyzed. To explain the coupling mechanism, an extended temporal coupled-mode model is established to provide the physical insight. The spectral response obtained from the model matches well with the numerical one. Due to the decoupled nature of the FRs, a self-calibrated or dual-parameter sensing scheme for refractive index and temperature is proposed. The refractive index sensitivity up to 765 nm/RIU and temperature sensitivity up to 0.087 nm/°C are obtained by wavelength interrogation with figure-of-merit (FOM) up to 33260.9 RIU-1 and 3.78 °C-1 respectively. The proposed sensor provides great potential in fields of the multi-parameter sensing.

Cloaking object on an optofluidic chip: its theory and demonstration.

Recently, the design of metamaterial guided by transformation optics (TO) has emerged as an effective method to hide objects from optical detection, based on arranging a bended light beam to detour. However, this TO-based solution involves fabrication of material with complicated distribution of permittivity and permeability, and the device falls short of tunability after fabrication. In this work, we propose an optofluidic model employing the method of streamline tracing-based transformation optofluidics (STTOF) to hydrodynamically reconfigure light propagation in a given flow field for object-cloaking purposes. The proof-of-concept is demonstrated and tested on an optofluidic chip to validate our proposed theory. Experimental results show that our proposed STTOF method can be used to successfully detour the light path from the object under cloaking in a mathematically pre-defined manner.

Reconfigurable multiwavelength fiber laser based on multimode interference in highly germanium-doped fiber.

A reconfigurable multiwavelength erbium-doped fiber laser based on an all-fiber multimode interferometer (MMI) is proposed and experimentally demonstrated. The interferometer is constructed by sandwiching a section of highly germanium-doped fiber (HGDF) between two sections of single-mode fiber. The insertion loss of the interferometer is as low as 2 dB. Due to the polarization-dependent spectral filtering effect formed by the MMI, by rotating the intracavity polarization controller, the laser output can be switched among single-, dual-, and triple-wavelength lasing states with optical signal-to-noise ratio up to 50 dB. In particular, the obtained dual-wavelength state shows high stability with wavelength shift within $ \pm {0.04}\;{\rm nm}$±0.04nm, wavelength spacing variation within $ \pm {0.03}\;{\rm nm}$±0.03nm, and power fluctuation within $ \pm {0.04}\;{\rm dB}$±0.04dB by monitoring the output spectra over 8 h at room temperature. By changing the length of the HGDF, the wavelength spacing can also be flexibly manipulated. Taking the advantages of reconfiguration, low cost, and easy fabrication, this fiber laser may have great potential in various optical applications.

Optofluidic refractive index sensor based on asymmetric diffraction.

A novel optofluidic refracrtive index (RI) sensor was proposed based on asymmetric Fraunhofer diffraction. In-plane optofluidic lens, light source, slit, diffraction pattern visualization zone and optical path were integrated into the microfluidic networks to avoid the manual alignment of the optical components as well as to reduce the cost of external bulky components. Unlike the conventional RI sensor, this device visualizes the bulk refractive index change of the liquid through a diffraction image, which is readily read-out for clinical diagnosis right at the point-of-care or on-site security check. In the experiment, the device can measure a RI change of as low as ~10-5 RIU. A low noise-equivalent detection limit (NEDL) of ~10-6 refractive index unit (RIU) and high sensitivity of ~1.1 × 104/RIU were achieved. The new device is practical and suitable to be extended for high throughput applications by simultaneously reading multiple chips with an 2D-array image sensor.

State of the Art and Perspectives on Silicon Photonic Switches.

In the last decade, silicon photonic switches are increasingly believed to be potential candidates for replacing the electrical switches in the applications of telecommunication networks, data center and high-throughput computing, due to their low power consumption (Picojoules per bit), large bandwidth (Terabits per second) and high-level integration (Square millimeters per port). This review paper focuses on the state of the art and our perspectives on silicon photonic switching technologies. It starts with a review of three types of fundamental switch engines, i.e., Mach-Zehnder interferometer, micro-ring resonator and micro-electro-mechanical-system actuated waveguide coupler. The working mechanisms are introduced and the key specifications such as insertion loss, crosstalk, switching time, footprint and power consumption are evaluated. Then it is followed by the discussion on the prototype of large-scale silicon photonic fabrics, which are based on the configuration of above-mentioned switch engines. In addition, the key technologies, such as topological architecture, passive components and optoelectronic packaging, to improve the overall performance are summarized. Finally, the critical challenges that might hamper the silicon photonic switching technologies transferring from proof-of-concept in lab to commercialization are also discussed.

An opto-acousto-fluidic microscopic system with a high spatiotemporal resolution for microfluidic applications.

In this work, we develop a new opto-acouto-fludic microsopic system, which employs a high-speed one-dimensional galvanometer scanner and an ultrafast pulse laser (600 kHz). The new system has achieved a high two-dimensional frame rate of up to 2500 Hz with a lateral resolution of 1.7 µm and an axial resolution of 36 µm at the imaging plane. To demonstrate the improved performance of the new system compared to our previous one, we carried out experiments to image the flowing droplets generated with T-junction and flow focusing configurations. We also successfully imaged dynamic migration of magneto particles subjected to non-uniform magnetic field in the microchannel. The results suggest that our new system has sufficient spatiotemporal resolutions to carry out studies for high throughput microfluidic applications.

Opto-acousto-fluidic microscopy for three-dimensional label-free detection of droplets and cells in microchannels.

This paper reports a novel method, opto-acousto-fluidic microscopy, for label-free detection of droplets and cells in microfluidic networks. Leveraging the optoacoustic effect, the microscopic system possesses capabilities of visualizing flowing droplets, analyzing droplet contents, and detecting cell populations encapsulated in droplets via the sensing of acoustic waves induced by the intrinsic light-absorbance of matter.

Photoacoustic endomicroscopy based on a MEMS scanning mirror.

In this Letter, we present a high-resolution photoacoustic endomicroscopy probe based on a microelectromechanical systems (MEMS) scanning mirror. The built-in optical assembly consists of a 0.7 mm graded-index (GRIN) lens for light focusing and a ϕ1 mm MEMS mirror to reflect and scan the beam. A miniaturized unfocused ultrasound transducer with a center frequency of 10 MHz is used for photoacoustic detection. Sharp blades, carbon fibers, and black tapes were utilized to evaluate the performance of the system. In vivo mouse ears and resected rectums were imaged to further demonstrate the feasibility of this probe for potential biological and clinical applications.

Characterization and optimization of illumination vector for contouring surface form and feature using DSPI.

Surface defect or damage is one of the critical factors leading to the failure of engineering materials and structures. The methodologies for the measurement of surface shape and feature or defect have been extensively explored and developed over the past few decades, including both contact and non-contact methods. Speckle pattern interferometry, as a non-contact optical method, has been demonstrated to effectively contour the surface shape through adjusting the illumination vector. However, few studies have been made to investigate the effect of the initial position of the illumination source as well as the source translation direction. In this paper, we report to carry out a study of measuring the surface form and feature using digital speckle pattern interferometry system via a slight translation of illumination source. Through theoretically analyzing the sensitivity factor along with the experimental validation, it is shown that the contouring fringe is more sensitive to the surface height with an off-axis illumination than the paraxial illumination. It is also found that translating the source along axial and lateral direction can be both used for the surface shape re-construction.

Confocal photoacoustic microscopy using a single multifunctional lens.

Photoacoustic microscopy (PAM) has remained one of the fastest developing biomedical imaging modalities in the past decade. The confocal strategy of optical illumination and acoustic detection is a way to boost the sensitivity of PAM. To achieve confocal PAM, current PAM systems utilize separate acoustic and optical converging devices, making the systems bulky and complicated. In this Letter, we demonstrate the use of a single-liquid lens to successfully achieve acoustic and optical confocal configuration for optical-resolution PAM (ORPAM). Using the lens with a numerical aperture of 0.43, we show that the resolution of the ORPAM system is 4.8 µm with a significantly improved sensitivity of acoustic detection. We also apply this compact ORPAM system to in vivo imaging of the vasculature of a rat ear.

Liquid acoustic lens for photoacoustic tomography.

Recently, intensive research has been conducted to accelerate the development of photoacoustic (PA) imaging modality for biomedical applications. The use of acoustic lenses to collect ultrasound signals is of great interest. This Letter presents the design and fabrication of a liquid acoustic diverging lens, which can enlarge the acceptance angle of an ultrasound transducer. This lens possesses an inherent advantage of low acoustic impedance and the convenience to be attached to or detached from a commercial flat transducer. Phantom experiments have been carried out to demonstrate the improvement of using such a liquid lens over using a bare transducer for PA tomography.

An electrokinetically tunable optofluidic bi-concave lens.

This paper numerically and experimentally investigates and demonstrates the design of an optofluidic in-plane bi-concave lens to perform both light focusing and diverging using the combined effect of pressure driven flow and electro-osmosis. The concave lens is formed in a rectangular chamber with a liquid core-liquid cladding (L(2)) configuration. Under constant flow rates, the performance of the lens can be controlled by an external electric field. The lens consists of a core stream (conducting fluid), cladding streams (non-conducing fluids), and auxiliary cladding streams (conducting fluids). In the focusing mode, the auxiliary cladding stream is introduced to sandwich the biconcave lens to prevent light rays from scattering at the rough chamber wall. In the diverging mode, the auxiliary cladding liquid has a new role as the low refractive-index cladding of the lens. In the experiments, the test devices were fabricated in polydimethylsiloxane (PDMS) using the standard soft lithography technique. Ethanol, cinnamaldehyde, and a mixture of 73.5% ethylene glycol and 26.5% ethanol work as the core stream, cladding streams and auxiliary cladding streams. In the numerical simulation, the electric force acts as a body force. The governing equations are solved by a finite volume method on a Cartesian fixed staggered grid. The evolution of the interface was captured by the level set method. The results show that the focal length in the focusing mode and the divergent angle of the light beam in the diverging mode can be tuned by adjusting the external electric field at fixed flow rates. The numerical results have a reasonable agreement with the experimental results.