Preface 1. Wave Theory of Optical Waveguides 2. Planar Optical Waveguides 3. Optical Fibers 4. Couple Mode Theory 5. Nonlinear Optical Effects in Optical Fibers 6. Finite Element Method 7. Beam Propagation Method 8. Staircase Concatention Method 9. Planar Lightwave Circuits 10. Theorems and Formulas Appendix

Fundamentals of optical waveguides

The past two decades have witnessed the revolutionary development of optical trapping of nanoparticles, most of which deal with trapping stiffness larger than 10-8 N/m. In this conventional regime, however, it remains a formidable challenge to sort out sub-50-nm nanoparticles with single-nanometer precision, isolating us from a rich flatland with advanced applications of micromanipulation. With an insightfully established roadmap of damping, the synchronization between optical force and flow drag force can be coordinated to attempt the loosely overdamped realm (stiffness, 10-10 to 10-8 N/m), which has been challenging. This paper intuitively demonstrates the remarkable functionality to sort out single gold nanoparticles with radii ranging from 30 to 50 nm, as well as 100- and 150-nm polystyrene nanoparticles, with single nanometer precision. The quasi-Bessel optical profile and the loosely overdamped potential wells in the microchannel enable those aforementioned nanoparticles to be separated, positioned, and microscopically oscillated. This work reveals an unprecedentedly meaningful damping scenario that enriches our fundamental understanding of particle kinetics in intriguing optical systems, and offers new opportunities for tumor targeting, intracellular imaging, and sorting small particles such as viruses and DNA.

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Nanometer-precision linear sorting with synchronized optofluidic dual barriers

Applications of fiber-optic biochemical sensor in microfluidic chips: A review.

Cell separation is a key step in many biomedical research areas including biotechnology, cancer research, regenerative medicine, and drug discovery. While conventional cell sorting approaches have led to high-efficiency sorting by exploiting the cell's specific properties, microfluidics has shown great promise in cell separation by exploiting different physical principles and using different properties of the cells. In particular, label-free cell separation techniques are highly recommended to minimize cell damage and avoid costly and labor-intensive steps of labeling molecular signatures of cells. In general, microfluidic-based cell sorting approaches can separate cells using "intrinsic" (e.g., fluid dynamic forces) versus "extrinsic" external forces (e.g., magnetic, electric field, etc.) and by using different properties of cells including size, density, deformability, shape, as well as electrical, magnetic, and compressibility/acoustic properties to select target cells from a heterogeneous cell population. In this work, principles and applications of the most commonly used label-free microfluidic-based cell separation methods are described. In particular, applications of microfluidic methods for the separation of circulating tumor cells, blood cells, immune cells, stem cells, and other biological cells are summarized. Computational approaches complementing such microfluidic methods are also explained. Finally, challenges and perspectives to further develop microfluidic-based cell separation methods are discussed.

Microfluidic‐Based Approaches in Targeted Cell/Particle Separation Based on Physical Properties: Fundamentals and Applications

The manipulation of cells and particles suspended in viscoelastic fluids in microchannels has drawn increasing attention, in part due to the ability for single-stream three-dimensional focusing in simple channel geometries. Improvement in the understanding of non-Newtonian effects on particle dynamics has led to expanding exploration of focusing and sorting particles and cells using viscoelastic microfluidics. Multiple factors, such as the driving forces arising from fluid elasticity and inertia, the effect of fluid rheology, the physical properties of particles and cells, and channel geometry, actively interact and compete together to govern the intricate migration behavior of particles and cells in microchannels. Here, we review the viscoelastic fluid physics and the hydrodynamic forces in such flows and identify three pairs of competing forces/effects that collectively govern viscoelastic migration. We discuss migration dynamics, focusing positions, numerical simulations, and recent progress in viscoelastic microfluidic applications as well as the remaining challenges. Finally, we hope that an improved understanding of viscoelastic flows in microfluidics can lead to increased sophistication of microfluidic platforms in clinical diagnostics and biomedical research. Insights into the dynamic behavior of biological fluids on the microscale are enabling more efficient analysis of cells, bacteria, and other small biological particles for research and clinical diagnostics. Blood, saliva and other biofluids have viscoelastic properties, which means that they exhibit both viscous and elastic behaviors depending on the forces to which they are subjected. These properties shape the migration behaviors of suspended bioparticles in unique ways. Jian Zhou and Ian Papautsky of the University of Illinois at Chicago have reviewed current progress in understanding the migration behaviors in such fluids within microfluidic devices. The authors discuss design principles that have enabled the development of microfluidic systems capable of separating and purifying cells, bacteria, and small vesicles from highly heterogeneous biological specimens, and highlight future challenges that need to be addressed.

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Viscoelastic microfluidics: progress and challenges.

Real-time detection of phosphate has significant meaning in marine environmental monitoring and forecasting the occurrence of harmful algal blooms. Conventional monitoring instruments are dependent on artificial sampling and laboratory analysis. They have various shortcomings for real-time applications because of the large equipment size and high production cost, with low target selectivity and the requirement of time-consuming procedures to obtain the detection results. We propose an optofluidic miniaturized analysis chip combined with micro-resonators to achieve real-time phosphate detection. The quantitative water-soluble components are controlled by the flow rate of the phosphate solution, chromogenic agent A (ascorbic acid solution) and chromogenic agent B (12% ammonium molybdate solution, 80% concentrated sulfuric acid and 8% antimony potassium tartrate solution with a volume ratio of 80 : 18 : 2). Subsequently, an on-chip Fabry–Perot microcavity is formed with a pair of aligned coated fiber facets. With the help of optical feedback, the absorption of phosphate can be enhanced, which can avoid the disadvantages of the macroscale absorption cells in traditional instruments. It can also overcome the difficulties of traditional instruments in terms of size, parallel processing of numerous samples and real-time monitoring, etc. The absorption cell length is shortened to 300 μm with a detection limit of 0.1 μmol L−1. The time required for detection is shortened from 20 min to 6 seconds. Predictably, microsensors based on optofluidic technology will have potential in the field of marine environmental monitoring.

Optofluidic marine phosphate detection with enhanced absorption using a Fabry–Pérot resonator

Leukocyte subpopulations contain crucial physiological information; hence, precise and specific leukocyte separation is very important for leukemia diagnosis and analysis. However, conventional centrifugation and immunofluorescence-based separation methods are inaccurate and inconvenient due to the overlapping cell size and density or complex marking processes. Herein, we report a new label-free technology for precise leukocyte subpopulation separation by synergy of acoustic and optical technologies. Standing surface acoustic wave (SSAW) solved the problem of gentle and precise focusing of cells in optical systems. In addition, SSAW was used for the separation of granulocytes, which have evident size distinction from other components. In case of lymphocytes and monocytes, which have overlap in size/density, optical force could distinguish them accurately based on the RI difference, with the convenience of acoustic pre-focusing. In this experiment, separation of three types of leukocyte subtypes with considerable throughput and purity was conducted, through which we obtained 99% pure lymphocytes, 98% pure monocytes, and 95% pure granulocytes. Experimental results prove that the device has robust ability in separating leukocyte phenotypes and have the advantages of being non-invasive, label-free and precise. In the future, this convenient hybrid method will be a potential powerful tool for auxiliary clinical diagnosis and analysis.

Precise label-free leukocyte subpopulation separation using hybrid acoustic-optical chip

Precise sorting of gold nanoparticles is important, but it still remains a big challenge. Traditional methods such as centrifugation can separate nanoparticles with a high throughput but at the cost of low precision. Optical tweezers enable the precise manipulation of a single nanoparticle in steady liquid environments. However, this method may become problematic when dealing with a considerable amount of nanoparticles in a flowing system due to the difficulties in balancing the additional Stokes forces by the fast velocity of streams and in controlling all dispersed nanoparticles with disorderly positions. Here, we exploit optical and hydrodynamic forces to sort gold nanoparticles in the flowing system, obtaining simultaneously high precision and considerable throughput. This is accomplished by utilizing opposite impinging streams to generate a stagnation point, near which the flow velocity becomes very small to reduce the Stokes force and to prolong the optical acting time. Nanoparticles of different si...

Precise Sorting of Gold Nanoparticles in a Flowing System

Optofluidics is a rising technology that combines microfluidics and optics. Its goal is to manipulate light and flowing liquids on the micro/nanoscale and exploiting their interaction in optofluidic chips. The fluid flow in the on-chip devices is reconfigurable, non-uniform and usually transports substances being analyzed, offering a new idea in the accurate manipulation of lights and biochemical samples. In this paper, we summarized the light modulation in heterogeneous media by unique fluid dynamic properties such as molecular diffusion, heat conduction, centrifugation effect, light-matter interaction and others. By understanding the novel phenomena due to the interaction of light and flowing liquids, quantities of tunable and reconfigurable optofluidic devices such as waveguides, lenses, and lasers are introduced. Those novel applications bring us firm conviction that optofluidics would provide better solutions to high-efficient and high-quality lab-on-chip systems in terms of biochemical analysis and environment monitoring.

Optofluidics: the interaction between light and flowing liquids in integrated devices

Conventional flow cytometry (FC) suffers from the diffraction limit for the detection of nanoparticles smaller than 100 nm, whereas traditional total internal reflection (TIR) microscopy can only detect few samples near the solid-liquid interface mostly in static states. Here we demonstrate a novel on-chip optofluidic technique using evanescent wave sensing for single nanoparticle real time detection by combining hydrodynamic focusing and TIR using immiscible flows. The immiscibility of the high-index sheath flow and the low-index core flow naturally generate a smooth, flat and step-index interface that is ideal for the TIR effect, whose evanescent field can penetrate the full width of the core flow. Hydrodynamic focusing can focus on all the nanoparticles in the extreme centre of the core flow with a width smaller than 1 μm. This technique enables us to illuminate every single sample in the running core flow by the evanescent field, leaving none unaffected. Moreover, it works well for samples much smaller than the diffraction limit. We have successfully demonstrated the scattering imaging and counting of 50 nm and 100 nm Au nanoparticles and also the fluorescence imaging and counting of 200 nm beads. The effective counting speeds are estimated as 1500, 2300 and 2000 particles per second for the three types of nanoparticles, respectively. The optical scattering spectra were also measured to determine the size of individual Au nanoparticles. This provides a new technique to detect nanoparticles and we foresee its application in the detection of molecules for biomedical analyses.

Xiaoqiang Zhu

Papers

Optofluidic marine phosphate detection with enhanced absorption using a Fabry–Pérot resonator

Precise label-free leukocyte subpopulation separation using hybrid acoustic-optical chip

Precise Sorting of Gold Nanoparticles in a Flowing System

Optofluidics: the interaction between light and flowing liquids in integrated devices

Optofluidic restricted imaging, spectroscopy and counting of nanoparticles by evanescent wave using immiscible liquids.