Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> We have demonstrated fluorescent liquid-core/air-cladding (LA) waveguides suitable for use as integrated optofluidic light sources. These waveguides were fabricated by conventional soft lithography using poly(dimethylsiloxane) (PDMS). Two-phase stratified flows of air and ethylene glycol with fluorescent dye were generated along the PDMS channel. Compared to the liquid-core/liquid-cladding (L(2)) waveguide, the larger refractive index contrast of the LA waveguide resulted in stronger optical confinement. Specifically, the larger refractive index contrast led to experimentally achievable captured fractions (the amount of light to be coupled into the liquid core) as high as 22.8% and the measured propagation losses as low as 0.14 dB cm(-1). Furthermore, in our LA waveguides, diffusional mixing of the core and cladding fluids did not occur and the size of the core stream could be reversibly tuned simply by adjusting the flow rates of the two contiguous phases. <s> BIB001 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> 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–Perot 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. <s> BIB002 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> We present a sandwich liquid-core waveguide for the study of the dynamic extraction of dye molecules by ionic liquid (IL). The incident light was introduced into the core of the IL phase directly via a fused silica prism to form total reflection at the IL/cladding interface. The changes in light intensity and absorbance spectra over time were monitored during the extraction process by maintaining an optical focus on the IL/water interface. The dynamic extraction of the dye Eriochrome Black-T (EBT) by the IL 1-n-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) at different concentrations and various pH conditions was investigated. The results indicated that the accumulation of the dye at the IL/water interface and the dynamic extraction of the dye into the IL phase both contributed to the increase in absorbance. The increased signal along with the increase in pH suggests that electrostatic interaction might be the main driving force for the extraction of EBT by BmimPF6, and the micro-circumstance provided by IL also has a decisive effect on the characteristics of the spectra recorded by the waveguide system. <s> BIB003 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> 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. <s> BIB004 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> Fabrication and performance of a functional photonic-microfluidic flow cytometer is demonstrated. The devices are fabricated on a Pyrex substrate by photolithographically patterning the microchannels and optics in a SU-8 layer that is sealed via a poly(dimethylsiloxane) (PDMS) layer through a unique chemical bonding method. The resulting devices eliminate the free-space excitation optics through integration of microlenses onto the chip to mimic conventional cytometry excitation. Devices with beam waists of 6 μm and 12 μm in fluorescent detection and counting tests using 2.5 and 6 μm beads-show CVs of 9%–13% and 23% for the two devices, respectively. These results are within the expectations for a conventional cytometer (5%–15%) and demonstrate the ability to integrate the photonic components for excitation onto the chip and the ability to maintain the level of reliable detection. <s> BIB005 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> Laser light is injected in a free standing hori-zontal draining soap lm through the glass frame sustain-ing the lm. Two propagation regimes are clearly identi-ed depending on the lm thickness. At the beginning of the drainage, the soap lm behaves as a multimode-one dimensional optoouidic waveguide. In particular, we ob-serve that the injected light creates a bottleneck in the lm and part of the injected light is refracted leading to whiskers. At the end of the drainage where the lm thick-ness is below µm, there is a strong selection among the various possible optical modes in the lm, and part of the light is deeected. This leads to a self selection of the mode propagation inside the lm. <s> BIB006 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> Abstract We report on the fabrication and characterization of versatile light waveguides exploiting filaments of a polar liquid confined within hydrophobic silica aerogels. Aerogels are highly porous materials with extremely low refractive index which makes them suitable as rigid cladding of liquid-core optofluidic waveguides based on total internal reflection of light. In this article, we introduce a new microfabrication technique that allows direct and precise processing of monolithic silica aerogels by ablation with femtosecond laser pulses. Using fast scanning of the focused laser ablation beam synchronized with the motion of the processed aerogel sample, we created high-quality straight microchannels of ∼5 mm length with controlled cross-sections inside monolithic aerogels. After the ablation, we filled the channels with high-refractive index ethylene glycol, forming multimode liquid core – solid cladding optofluidic waveguides. Subsequently, we carried out light-guiding experiments to measure overall optical attenuation of these waveguides. The characterization of waveguide transmission yielded values of propagation losses lower than 10 dB cm - 1 , demonstrating that the liquid-core waveguides with laser-ablated aerogel cladding represent an attractive alternative in optofluidic applications targeting controlled routing of light along arbitrary three-dimensional paths. <s> BIB007 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> Multimode interference (MMI) is a typical self-imaging phenomenon and has been widely exploited for optical devices like couplers and splitters. Usually, it utilizes solid waveguides only and thus has very limited tunability in self-imaging properties. This paper reports our original work on tunable MMI using a hybrid optofluidic waveguide. It is generated by the diffusion between miscible flows in a microchannel and consists of two parts: gradient-index liquid–liquid waveguide for light modulation and step-index liquid–solid waveguide for image formation. Simulation and experiments have shown successful realization of the real-time tuning of self-imaging properties. For detail, the image point (focal spot) width could be modulated from 7 μm to 16 μm, and the self-imaging period changes in the range of 500 μm by varying the fluid properties. It is foreseeable that such a hybrid optofluidic waveguide may find wider applications in lab-on-a-chip systems and optical devices. <s> BIB008 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> This paper describes the realization of highly sensitive surface-enhanced Raman spectroscopy (SERS) via an integrated three-dimensional liquid-core/liquid-cladding waveguide. The cladding flow enclosed the core flow in both the horizontal and vertical directions within a single-layered microfluidic channel, and the laser beam was guided through the core stream. Deionized water was used to suspend SERS-active silver nanocolloids to form the core fluid, and 2,2,2-trifluoroethanol was used as the cladding fluid. Dipicolinic acid, commonly used as a biomarker for the detection of Bacillus anthracis, was employed as the target analyte. The sensitivity of the SERS signal was enhanced through this design because the signals backscattered from the analytes accumulated along the core stream and increased the SERS detection volume. The SERS data was evaluated in terms of the analyte concentration in the core fluid, the irradiated laser power, and the cross-sectional area of the core stream. The present data were compared with a conventional SERS detection approach in order to quantify the enhancement factor. The detection limit of concentration, 50 nM at an acquisition time of 6 s, was a factor of 35 smaller than that of conventional methods. <s> BIB009 </s> Optofluidic Device Based Microflow Cytometers for Particle/Cell Detection: A Review <s> Waveguides <s> An electrically reconfigurable liquid-core/liquid-cladding (L2) optical waveguide with core liquid γ-butyrolactone (GBL, ncore = 1.4341, ecore = 39) and silicone oil (ncladding = 1.401, ecladding = 2.5) as cladding liquid is accomplished using dielectrophoresis (DEP) that attracts and deforms the core liquid with the greater permittivity to occupy the region of strong electric field provided by Teflon-coated ITO electrodes between parallel glass plates. Instead of continuously flowing core and cladding liquids along a physical microchannel, the DEP-formed L2 optical waveguide guides light in a stationary virtual microchannel that requires liquids of limited volume without constant supply and creates stable liquid/liquid interfaces for efficient light guidance in a simply fabricated microfluidic device. We designed and examined (1) stationary and (2) moving L2 optical waveguides on the parallel-plate electromicrofluidic platform. In the stationary L-shaped waveguide, light was guided in a GBL virtual microchannel core for a total of 27.85 mm via a 90° bend (radius 5 mm) before exiting from the light outlet of cross-sectional area 100 μm × 100 μm. For the stationary spiral waveguide, light was guided in a GBL core containing Rhodamine 6G (R6G, 1 mM) and through a series of 90° bends with decreasing radii from 5 mm to 2.5 mm. With the stationary straight waveguide, the propagation loss was measured to be 2.09 dB cm−1 in GBL with R6G (0.01 mM). The moving L-shaped waveguide was implemented on a versatile electromicrofluidic platform on which electrowetting and DEP were employed to generate a precise GBL droplet and form a waveguide core. On sequentially applying appropriate voltage to one of three parallel L-shaped driving electrodes, the GBL waveguide core was shifted; the guided light was switched at a speed of up to 0.929 mm s−1 (switching period 70 ms, switching rate 14.3 Hz) when an adequate electric signal (173.1 VRMS, 100 kHz) was applied. <s> BIB010
Optofluidic waveguides, such as solid-core/liquid-cladding waveguides (SCLC), liquid-core waveguides (LCW) BIB007 BIB010 and hybrid core waveguides (HCW) BIB003 BIB008 , have been reported. Guiding of the light is ensured if the refractive index of the core material is higher than that of the cladding. In an optofluidic microflow cytometer, deionized (DI) water, water-based liquids and organic-based liquids are typically used for cladding materials, while glasses, polymers and semiconductors are typical materials used for the core. Choi et al. BIB009 used DI water as a core fluid and 2,2,2-trifluoroethanol as cladding fluid to form a waveguide. Liquid-core/air-cladding (LA) waveguides have been integrated into an optofluidic device by Lim et al. BIB001 . Shi et al. BIB008 demonstrated a hybrid waveguide consisting of a liquid-liquid waveguide and a liquid-solid waveguide to achieve real-time self-imaging in a microchannel. Compared to 2D liquid-liquid waveguide, the 3D liquid-liquid waveguide is surrounded by cladding fluid in both directions, and the confinement of light is better BIB002 . Yang et al. demonstrated bending and manipulating light via optofluidic waveguides with their unique optical properties BIB004 . Optically transparent photoresists, such as SU-8, are widely used to fabricate on-chip waveguides integrated simultaneously with the microfluidic channel during the fabrication process BIB005 . SU-8 can function as the core while voids provide air to function as cladding material. As the refractive index of SU-8 (about 1.59) is higher than that of the air, strong optical confinement is observed, lowering the background noise  . Figure 5a shows a typical air cladding SU-8 core waveguide fabricated by Watts et al.  . Light is guided through the long straight waveguide to the lens system, shaping in the microchannel and then collected by multiple waveguides at angles at 5°, 30°and 75°to the input laser beam axis. FSC, FL and SSC are collected from each of the angled waveguides (respectively), where the angled on-chip waveguides help to avoid noise due to a couple of stray light signals from the input laser diode. To further improve the signal to noise ratio (SNR), an angled input waveguide along with an angled lens system were used to reduce the noise by allowing a full 90°angle between the input and SSC, as shown in Figure 5b . A low background noise is created for SSC, which has the same wavelength as that of the excitation beam. Waveguides made by optically transparent polymers, such as poly(dimethylsiloxane) (PDMS), can also be integrated onto the device. In addition to polymers and photoresists, researchers have shown that other materials can also function as waveguides. For example, Emile et al. BIB006 used 1D soap films as waveguides to guide light coming from a laser diode. 