Micro-optofluidic switch realized by 3D printing technology

This paper presents a PDMS micro-optofluidic chip that allows a laser beam to be driven directly toward a two-phase flow stream in a micro-channel while at the same time automatically, detecting the slug’s passage and stirring the laser light, without the use of any external optical devices. When the laser beam interacts with the microfluidic flow, depending on the fluid in the channel and the laser angle of incidence, a different signal level is detected. So a continuous air–water segmented flow will generate a signal that switches between two values. The device consists of a T-junction, which generates the two-phase flow, and three optical fiber insertions, which drive the input laser beam toward a selected area of the micro-channel and detects the flow stream. Three micro-channel sections of different widths were considered: 130, 250, 420 μm and the performance of the models was obtained by comparing ray-tracing simulations. The master of the device has been realized by 3D printing technology and a protocol which realizes the PDMS chip is presented. The static and dynamic characterizations, considering both single flows and two-phase flows, were carried out, and in spite of the device’s design simplicity, the sensitivity of the system to capture changes in the segmented flows and to stir the laser light in different directions was fully confirmed. The experimental tests show the possibility of obtaining satisfactory results with channel diameters in the order of 200 μm.     

Experimental study of diffusion-based extraction from a cell suspension

A recently proposed application of microfluidics is the post-thaw processing of biological cells. Numerical simulations suggest that diffusion-based extraction of the cryoprotective agent dimethyl sulfoxide (DMSO) from blood cells is viable and more efficient than centrifugation, the conventional method of DMSO removal. In order to validate the theoretical model used in these simulations, a prototype was built and the flow of two parallel streams, a suspension of Jurkat cells containing DMSO and a wash stream that contained neither cells nor DMSO, was characterized experimentally. DMSO transport in a rectangular channel (depth 500 μm, width 25 mm and overall length 125 mm) was studied as a function of three dimensionless parameters: depth ratio of the streams, cell volume fraction in the cell solution, and the Peclet number (Pe) based on channel depth, average flow rate and the diffusion coefficient for DMSO in water. In our studies, values of Pe ranged from O(10³) to O(10⁴). Laminar flow was ensured by keeping the Reynolds number between O(1) and O(10). Experimental results based on visual and quantitative data demonstrate conclusively that a microfluidic device can effectively remove DMSO from liquid and cell laden streams without compromising cell recovery. Also, flow conditions in the microfluidic device appear to have no adverse effect on cell viability at the outlet. Further, the results demonstrate that we can predict the amount of DMSO removed from a given device with the theoretical model mentioned previously.     

Fabrication of circular microfluidic channels through grayscale dual-projection lithography

Circular microfluidic channels are in great demand since they are more realistic in mimicking physiological flow systems, generating axis-symmetrical flow, and achieving uniform shear stress. A typical microchannel with rectangular cross section can induce non-physiological gradients of shear rate, pressure, and velocity. This paper presents a novel method of fabricating microfluidic channels with circular and elliptical cross sections through grayscale dual-projection lithography. Our method utilizes two projecting systems to expose grayscale image face-to-face and simultaneously polymerize the photocurable material. The cross-sectional profiles of the fabricated microchannels are consistent with mathematical predictions and, therefore, demonstrate the capability of controlling the channel shapes precisely. Customized circular microchannels can be generated with complex features such as junctions, bifurcations, hierarchies, and gradually changed diameters. This method is capable of fabricating circular channels with a wide range of diameters (39 μm–2 mm) as well as elliptical channels with a major-to-minor axis ratio up to 600%. Microfluidic devices with circular cross sections suitable for particle analysis were made as a demonstrative application in nanoparticle binding and distribution within a mimetic blood vessel. A ready-to-use microfluidic device with customized circular channels can be fabricated within 1 h without the need of clean room or expensive photolithography devices.     

Microfluidic encapsulation of cells in alginate particles via an improved internal gelation approach

An improved internal gelation approach is developed to encapsulate single mammalian cells in monodisperse alginate microbeads as small as 26 μm in diameter and at rates of up to 1 kHz with high cell viability. The cell damage resulting from contact with calcium carbonate nanoparticles as gelation reagents is eliminated by employing a co-flow microfluidic device, and the cell exposure to low pH is minimized by a chemically balanced off-chip gelation step. These modifications significantly improve the viability of cells encapsulated in gelled alginate particles. Two different mammalian cell types are encapsulated with viability of over 84 %. The cells are functional and continue to grow inside the microparticles.     

A silicone-based microfluidic chip grafted with carboxyl functionalized hyperbranched polyglycerols for selective protein capture

A poly(dimethylsiloxane) (PDMS)-based functional microfluidic device containing a charged matrix of PDMS pillar arrays grafted with hyperbranched polyglycerols (HPGs) was developed. Samples of PDMS were modified with allylamine plasma to form amine groups on the surface prior to the covalent grafting of succinimdyl ester-functionalized HPGs. The anionic functionality of the PDMS channel matrices was developed by altering the number of carboxyl groups present on the HPGs. The grafting of HPGs onto PDMS plates was investigated via contact angle measurement and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), while the grafting of the inside channel was investigated by electroosmotic flow (EOF) measurements. The charge density on grafted HPG was optimized to minimize the nonspecific protein adsorption and increase the selective capture of positively charged proteins. A proof-of-concept device was fabricated on PDMS and demonstrated that the device selectively captures positively charged protein (avidin) from a mixture of bovine serum albumin (BSA)-avidin at pH 7.4 in phosphate buffered saline (PBS). In order to increase the capture efficiency of the proteins in this PDMS-based device, pillar arrays have been fabricated within the channel. As a demonstration, the new device separated two proteins with an avidin capture efficiency of 100 ± 2.95% per 3 min from a 0.02 mg/ml protein solution (avidin:BSA wt ratio: 1:1). This new microfluidic-based device shows a great deal of promise as a tool for protein capture and analysis.     

Electro-adaptive microfluidics for active tuning of channel geometry using polymer actuators

With the expanding role of microfluidics in biology and medicine, methodologies for on-chip fluid sample manipulation become increasingly important. While conventional methods of microfluidic actuation, such as pneumatic and piezoelectric valves, are well characterized and commonly used, they require bulky external setups and complex fabrication. To address the need for a simple microfluidic actuator, we introduce a hybrid device consisting of an electroactive polymer that controls the shape of a microfluidic channel with an applied bias voltage. The electro-adaptive microfluidic (EAM) device allowed tuning of fluidic resistances by up to 18.1 %. In addition, we have shown that the EAM device is able to clear microchannel blockages by actively expanding the channel cross section. Biocompatibility tests show the EAM device has little effect on cell viability within a voltage range and thus has the potential to be utilized in bio-microfluidic systems. All of these results indicate that this EAM device design may find use in applications from cell sorting and trapping and self-clearing channels, to the reduction of lab-on-a-chip complexity via tunable channel geometries.     

Microfluidic fluorescence-activated cell sorting (μFACS) chip with integrated piezoelectric actuators for low-cost mammalian cell enrichment

A low-cost, microfluidic fluorescence-activated cell sorting (μFACS) microchip integrated with two piezoelectric lead–zirconate–titanate actuators was demonstrated for automated, high-performance mammalian cell analysis and enrichment. In this PDMS–glass device, cells were hydrodynamically focused into a single file line in the lateral direction by two sheath flows, and then interrogated with a forward scattering and confocal fluorescent detection system. The selected cells were displaced transversely into a collection channel by two piezoelectric actuators that worked in a pull–push relay manner with a minimal switching time of ~0.8 ms. High detection throughput (~2500 cells/s), high sorting rate (~1250 cells/s), and high sorting efficiency (~98%) were successfully achieved on the μFACS system. Six cell mixture samples containing 22.87% of GFP-expressing HeLa cells were consecutively analyzed and sorted on the chip, revealing a stable sorting efficiency of 97.7 ± 0.93%. In addition, cell mixtures containing 37.65 and 3.36% GFP HeLa cells were effectively enriched up to 83.82 and 78.51%, respectively, on the microchip, and an enrichment factor of 105 for the low-purity (3.36%) sample was successfully obtained. This fully enclosed, disposable microfluidic chip provides an automated platform for low-cost fluorescence-based cell detection and enrichment, and is attractive to applications where cross-contamination between runs and aerosol hazard are the primary concerns.     

Enhanced sample concentration on a three-dimensional origami paper-based analytical device with non-uniform assay channel

Traditional microfluidic paper-based analytical devices (μPADs) consist of a flat straight channel printed on a paper substrate. Such devices provide a promising low-cost solution for a variety of biomedical assays. However, they have a relatively high sample consumption due to their use of external reservoirs. Moreover, in μPADs based on the ion concentration polarization (ICP) effect, controlling the cross-sectional area of the Nafion membrane relative to that of the hydrophilic channel is difficult. Accordingly, the present study utilizes an origami technique to create a μPAD with a three-dimensional (3D) structure. The μPAD features short channels and embedded reservoirs, and therefore reduces both the driving voltage requirement and the sample consumption. Moreover, the preconcentration effect is enhanced through the use of an additional hydrophilic area adjacent to the Nafion membrane. The existence of electroosmotic flow (EOF) within the proposed device is confirmed using a current-monitoring method. In addition, the occurrence of ICP is evaluated by measuring the current–voltage response of the device at external voltages ranging from 0 to 50 V. The experimental results obtained for a fluorescein sample with an initial concentration of 10^?5 M show that a 100-fold enhancement factor can be achieved given the use of a non-uniform-geometry design for the assay channel and an additional hydrophilic region with an area equal to approximately 10% of the channel cross-sectional area. Finally, a 100-fold factor can also be achieved for a fluorescein isothiocyanate sample with an initial concentration of 10^?6 M given an external driving voltage of 40 V.     

Arrays of high-aspect ratio microchannels for high-throughput isolation of circulating tumor cells (CTCs)

Microsystem-based technologies are providing new opportunities in the area of in vitro diagnostics due to their ability to provide process automation enabling point-of-care operation. As an example, microsystems used for the isolation and analysis of circulating tumor cells (CTCs) from complex, heterogeneous samples in an automated fashion with improved recoveries and selectivity are providing new opportunities for this important biomarker. Unfortunately, many of the existing microfluidic systems lack the throughput capabilities and/or are too expensive to manufacture to warrant their widespread use in clinical testing scenarios. Here, we describe a disposable, all-polymer, microfluidic system for the high-throughput (HT) isolation of CTCs directly from whole blood inputs. The device employs an array of high aspect ratio (HAR), parallel, sinusoidal microchannels (25 × 150 μm; W × D; AR = 6.0) with walls covalently decorated with anti-EpCAM antibodies to provide affinity-based isolation of CTCs. Channel width, which is similar to an average CTC diameter (10–20 μm), plays a critical role in maximizing the probability of cell/wall interactions and allows for achieving high CTC recovery. The extended channel depth allows for increased throughput at the optimized flow velocity (2 mm/s in a microchannel); maximizes cell recovery, and prevents clogging of the microfluidic channels during blood processing. Fluidic addressing of the microchannel array with a minimal device footprint is provided by large cross-sectional area feed and exit channels poised orthogonal to the network of the sinusoidal capillary channels (so-called Z-geometry). Computational modeling was used to confirm uniform addressing of the channels in the isolation bed. Devices with various numbers of parallel microchannels ranging from 50 to 320 have been successfully constructed. Cyclic olefin copolymer (COC) was chosen as the substrate material due to its superior properties during UV-activation of the HAR microchannels surfaces prior to antibody attachment. Operation of the HT-CTC device has been validated by isolation of CTCs directly from blood secured from patients with metastatic prostate cancer. High CTC sample purities (low number of contaminating white blood cells) allowed for direct lysis and molecular profiling of isolated CTCs.     

SmCo micromolding in an aqueous electrolyte

The micromolding technique has been successfully applied to samarium–cobalt (SmCo) films electrodeposited in an aqueous solution. After optimization of the deposition conditions in a Hull cell, taking into account the supplying mode, the pulse time and the addition of supporting electrolyte, films with thickness between 1 and 1.5 μm have been patterned in 1 mm × 1 mm squares. Is has been found that high Sm/(Sm + Co) ratio can be obtained in direct current mode, with or without supporting electrolyte. In addition, the micromolding process reduces the contamination in oxygen due to oxidation and/or incorporation of precipitates, from 20 to 30 % in the Hull cell to 10–15 % in the pattern.     

Automating fluid delivery in a capillary microfluidic device using low-voltage electrowetting valves

A multilayer capillary polymeric microfluidic device integrated with three normally closed electrowetting valves for timed fluidic delivery was developed. The microfluidic channel consisted two flexible layers of poly (ethylene terephthalate) bonded by a pressure-sensitive adhesive spacer tape. Channels were patterned in the spacer tape using laser ablation. Each valve contained two inkjet-printed silver electrodes in series. Capillary flow within the microchannel was stopped at the second electrode which was modified with a hydrophobic monolayer (valve closed). When a potential was applied across the electrodes, the hydrophobic monolayer became hydrophilic and allowed flow to continue (valve opened). The relationship between the actuation voltage, the actuation time, and the distance between two electrodes was performed using a microfluidic chip containing a single microchannel design. The results showed that a low voltage (4.5 V) was able to open the valve within 1 s when the distance between two electrodes was 1 mm. Increased voltages were needed to open the valves when the distance between two electrodes was increased. Additionally, the actuation time required to open the valve increased when voltage was decreased. A multichannel device was fabricated to demonstrate timed fluid delivery between three solutions. Our electrowetting valve system was fabricated using low-cost materials and techniques, can be actuated by a battery, and can be integrated into portable microfluidic devices suitable for point-of-care analysis in resource-limited settings.     

Three-dimensional hydrodynamic flow and particle focusing using four vortices Dean flow

We present a three-dimensional (3D) hydrodynamic focusing device built on a single-layer platform using single sheath flow. Despite the simple structure and operation, the device not only achieves narrow focusing of a sample fluid or particles but also switches the cross-sectional size and lateral position of the sample stream. The focusing mechanism utilizes four Dean vortices generated in a high-speed flow through a curved channel. Theoretical calculations, numerical simulations, and an experimental study demonstrated that the device could focus microparticles that resemble human platelets in terms of particle size and density in a single-stream manner. Further simulation study suggested that the device could focus most cell sizes used in flow cytometry with a throughput of 200,000 cells s^?1. In addition, the device can function as a 3D liquid-core/liquid-cladding (L2) optical waveguide by introducing a core liquid with a refractive index higher than that of the cladding.     

A hybrid optical–mechanical calibration procedure for the Scalable-SPIDAR haptic device

In this research, a simple, yet, efficient calibration procedure is presented in order to improve the accuracy of the Scalable-SPIDAR haptic device. The two-stage procedure aims to reduce discrepancies between measured and actual values. First, we propose a new semi-automatic procedure for the initialization of the haptic device. To perform this initialization with a high level of accuracy, an infrared optical tracking device was used. Furthermore, audio and haptic cues were used to guide the user during the initialization process. Second, we developed two calibration methods based on regression techniques that effectively compensate for the errors in tracked position. Both neural networks and support vector regression methods were applied to calibrate the position errors present in the haptic device readings. A comparison between these two regression methods was carried out to show the underlying algorithm and to indicate the inherent advantages and limitations for each method. Initial evaluation of the proposed procedure indicated that it is possible to improve accuracy by reducing the Scalable-SPIDAR’s average absolute position error to about 6 mm within a 1 m × 1 m × 1 m workspace.     

Numerical simulation of the capillary flow in the meander microchannel

Pumping in microfluidic devices is an important issue in actuating fluid flow in microchannel, especially that capillary force has received more and more attractions due to the self-driven motion without external power input. However, less 2D simulation was done on the capillary flow in microchannel especially the meander microchannel which can be used for mixing and lab-on-a-chip (LOC) application. In this paper, the numerical simulation of the capillary flow in the meander microchannel has been studied using computer fluid dynamic simulation software CFD-ACE⁺. Different combinations of channel width in the X-direction denoted as W_x and Y-direction denoted as W_y were designed for simulating capillary flow behavior and pressure drop. The designed four types of meander microchannels (W_x × W_y) were 100 × 100 μm, 100 × 200 μm, 50 × 200 μm, and 50 × 400 μm. In this simulation results, it is found that the capillary pumping speed is highly depending on the channel width. The large speed change occurs at the turning angle of channel width change from W_x to W_y. The fastest pumping effect is found in the meander channel of 100 × 100 μm, which has an average pumping speed of 0.439 mm/s. The slowest average flow speed of 0.205 mm/s occurs in the meander channel of 50 × 400 μm. Changing the meander channel width may vary the capillary flow behavior including the pumping speed and the flow resistance as well as pressure drop which will be a good reference in designing the meander microchannels for microfluidic and LOC application.     

Design of microfluidic channels for magnetic separation of malaria-infected red blood cells

This study is motivated by the development of a blood cell filtration device for removal of malaria-infected, parasitized red blood cells (pRBCs). The blood was modeled as a multi-component fluid using the computational fluid dynamics discrete element method (CFD-DEM), wherein plasma was treated as a Newtonian fluid and the red blood cells (RBCs) were modeled as soft-sphere solid particles which move under the influence of drag, collisions with other RBCs, and a magnetic force. The CFD-DEM model was first validated by a comparison with experimental data from Han and Frazier (Lab Chip 6:265–273, 2006) involving a microfluidic magnetophoretic separator for paramagnetic deoxygenated blood cells. The computational model was then applied to a parametric study of a parallel-plate separator having hematocrit of 40 % with 10 % of the RBCs as pRBCs. Specifically, we investigated the hypothesis of introducing an upstream constriction to the channel to divert the magnetic cells within the near-wall layer where the magnetic force is greatest. Simulations compared the efficacy of various geometries upon the stratification efficiency of the pRBCs. For a channel with nominal height of 100 µm, the addition of an upstream constriction of 80 % improved the proportion of pRBCs retained adjacent to the magnetic wall (separation efficiency) by almost twofold, from 26 to 49 %. Further addition of a downstream diffuser reduced remixing and hence improved separation efficiency to 72 %. The constriction introduced a greater pressure drop (from 17 to 495 Pa), which should be considered when scaling up this design for a clinical-sized system. Overall, the advantages of this design include its ability to accommodate physiological hematocrit and high throughput, which is critical for clinical implementation as a blood-filtration system.     

Role of interface shape on the laminar flow through an array of superhydrophobic pillars

In this study, measurements of the pressure drop and the velocity vector fields through a regular array of superhydrophobic pillars were systematically taken to investigate the role of air–water interface shape on laminar drag reduction. A polydimethylsiloxane microfluidic channel was created with a regular array of apple-core-shaped and circular pillars bridging across the entire channel. Due to the shape and hydrophobicity of the apple-core-shaped pillars, air was trapped on the side of the pillars after filling the microchannel with water. The measurements were taken at a capillary number of Ca = 6.6 × 10^?5. The shape of the air–water interface trapped within the superhydrophobic apple-core-shaped pillars was systematically modified from concave to convex by changing the static pressure within the microchannel. The pressure drop through the microchannel containing the superhydrophobic apple-core-shaped pillars was found to be sensitive to the shape of the air–water interface. For static pressures which resulted in the apple-core-shaped superhydrophobic pillars having a circular cross section, D/D ₀ = 1, a drag reduction of 7% was measured as a result of slip along the air–water interface. At large static pressures, the interface was driven into the apple-core-shaped pillars, resulting in decrease in the effective size of the pillars and an increase in the effective spacing between pillars. When combined with a slip velocity measured to be 10% of the average velocity between the pillars, the result was a pressure drop reduction of 18% compared to the circular pillars at a non-dimensional interface diameter of D/D ₀ = 0.8. At low static pressures, the pressure drop increased significantly as the expanded air–water interface constricted flow through the array of pillars even as large interfacial slip velocity was maintained. At D/D ₀ = 1.1, for example, the pressure drop increased by 17% compared to the circular pillar. This drag increase was the result of an increased form drag due to a decrease in porosity and permeability of the pillar array and a decrease in the skin friction drag due to the presence of the air–water interface. For D/D ₀ = 1.1, the slip velocity was measured to be 45% of the average streamwise velocity between the pillars. When compared to no-slip pillars of similar shape, the drag reduction was found to increase from 6 to 9% with increasing convex curvature of the air–water interface.     

The manufacturing of packaged capillary action microfluidic systems by means of CO2 laser processing

In this article we demonstrate a simple yet robust rapid prototyping manufacturing technique for the construction of autonomous microfluidic capillary systems by means of CO₂ laser processing. The final packaging of the microfluidic device is demonstrated using thermal lamination bonding and allows for a turnaround time of approximately 30 min to 3 h from activation of the laser system to device use. The low-cost CO₂ laser system is capable of producing repeatable microfluidic structures with minimum feature sizes superior than 100–150 μm over channel depths of more than 100 μm. This system is utilised to create capillary pump and valve designs within poly (methyl methacrylate) (PMMA) substrates. Such components are part of advanced systems that can self initiate and maintain the flow of various volumes of fluids from an input to a collection reservoir, whilst also controlling the progression of the flow through the various demonstrated valve type structures. The resulting systems could prove a very useful alternative to traditional, non-integrated, fluidic actuation and flow control systems found on-chip, which generally require some form of energy input, have limited portable capabilities and require more complex fabrication procedures.     

One-step rapid fabrication of paper-based microfluidic devices using fluorocarbon plasma polymerization

In this work, we demonstrated an all-dry, top-down, and one-step rapid process to fabricate paper-based microfluidic devices using fluorocarbon plasma polymerization. This process is able to create fluorocarbon-coated hydrophobic patterns on filter paper substrates while maintaining the trench and detection regions intact and free of contamination after the fabrication process, as confirmed by attenuated total reflectance–Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. We have shown that the processing time is one critical factor that influences the device performance. For the device fabricated with a sufficiently long processing time (180 s), the sample fluid flow can be well confined in the patterned trenches. By testing the device with an 800 μm channel width, a sample solution amount as small as 4.5 μL is sufficient to perform the test. NO₂ ^? assay is also performed and shows that such a device is capable for biochemical analysis.     

Sorting algal cells by morphology in spiral microchannels using inertial microfluidics

Sub-millimetre phytoplankton (here referred to as algae) exist in a wide variety of shapes and sizes. Measuring algae morphology can be a useful tool for understanding the species dynamics in a body of water, and size-sorting in general is a valuable first step in automated species identification. Here, we demonstrate the sorting of algae by shape and size in a spiral microchannel, in which lift forces and Dean flow drag forces combine to position the cells in a shape-dependent location in the channel cross section. Three species were used for experiments: the high-aspect-ratio cylindrical Monoraphidium griffithii, the prolate spheroidal Cyanothece aeruginosa, and the small spherical Chlorella vulgaris. These results are compared with the sorting of similarly sized polystyrene latex microspheres in the same device over the same range of flow rates. Tests were done at conditions which yielded average Dean numbers over the channel length of 3 < De < 30. At 1.6 mL/min, the 10- and 20-µm microspheres could be separated with an efficiency of 96 %. The best sorting results for the algae were obtained at a flow rate of 3.2 mL/min, which yielded an average Dean number of De = 25 over the channel length. These conditions led to the separation of the Monoraphidium from the differently shaped Cyanothece; these two species could be sorted with a 77 % separation efficiency despite the relatively high polydispersity in cell sizes within each species. The elegance and simplicity of inertial microfluidics make it appropriate for the high-throughput pre-sorting of algae cells upstream of other integrated sensing modalities in a field-deployable device.     

Inertial focusing of microparticles in curvilinear microchannels with different curvature angles

Inertial microfluidics has become one of the emerging topics due to potential applications such as particle separation, particle enrichment, rapid detection and diagnosis of circulating tumor cells. To realize its integration to such applications, underlying physics should be well understood. This study focuses on particle dynamics in curvilinear channels with different curvature angles (280°, 230°, and 180°) and different channel heights (90, 75, and 60 µm) where the advantages of hydrodynamic forces were exploited. We presented the cruciality of the three-dimensional particle position with respect to inertial lift forces and Dean drag force by examining the focusing behavior of 20 µm (large), 15 µm (medium) and 10 µm (small) fluorescent polystyrene microparticles for a wide range of flow rates (400–2700 µL/min) and corresponding channel Reynolds numbers. Migration of the particles in lateral direction and their equilibrium positions were investigated in detail. In addition, in the light of our findings, we described two different regions: transition region, where the inner wall becomes the outer wall and vice versa, and the outlet region. The maximum distance between the tight particle stream of 20 and 15 µm particles was obtained in the 90 high channel with curvature angle of 280° at Reynolds number of 144 in the transition region (intersection of the turns), which was the optimum condition/configuration for focusing.