Fluidic Resistance Research Articles

A Pressure Driven Nanoconcentrator with Anti-Clogging Behavior for Recovery of Bio-Nanoparticles

This study proposes a counterflow nanoconcentrator (nC) with anti-clogging behavior as a concept for concentration of nano-sized particles, with the purpose of concentrating viruses in water samples and improving the sensitivity of subsequent detection. The nC incorporates penetrating nanochannels of varying cross section arranged between aerofoil-shaped micropillars distributed in an elliptical shape, with critical separation in the nanoscale. Continuum theory and discrete lattice Boltzmann method are used to describe the flow through channels at a critical width of 40 nm. Nanofluidic and microfluidic performance characteristics of the concentrator were investigated by simplifying the filtrate channels as effective fluidic lumped resistance elements. Comparison between nC units and microconcentrator units showed that the performance of the nC is consistent with that of the counterflow microconcentrator. But due to the large fluidic resistance exerted by the nC, operational parameter (pressure) and design parameters must be changed to preserve the anti-clogging behavior. Through a downscaling and a denser distribution of concentrating units compared with the microconcentrator, the results infer that the nC is capable of transporting a sufficient volume of liquid and is able to concentrate nanoparticles from water samples with reduced clogging risk and at high concentration efficiency.

Integration of lateral porous silicon membranes into planar microfluidics.

In this work, we present a novel fabrication process that enables the monolithic integration of lateral porous silicon membranes into single-layer planar microchannels. This fabrication technique relies on the patterning of local electrodes to guide pore formation horizontally within the membrane and on the use of silicon-on-insulator substrates to spatially localize porous silicon within the channel depth. The feasibility of our approach is studied by current flow analysis using the finite element method and supported by creating 10 μm long mesoporous membranes within 20 μm deep microchannels. The fabricated membranes are demonstrated to be potentially useful for dead-end microfiltration by adequately retaining 300 nm diameter beads while macromolecules such as single-stranded DNA and immunoglobulin G permeate the membrane. The experimentally determined fluidic resistance is in accordance with the theoretical value expected from the estimated pore size and porosity. The work presented here is expected to greatly simplify the integration of membranes capable of size exclusion based separation into fluidic devices and opens doors to the use of porous silicon in planar lab on a chip devices.

In vivo testing of a novel adjustable glaucoma drainage device.

We report on the in vivo testing of a novel noninvasively adjustable glaucoma drainage device (AGDD), which features an adjustable outflow resistance, and assess the safety and efficiency of this implant. Under general anesthesia, the AGDD was implanted on seven white New Zealand rabbits for a duration of 4 months under a scleral flap in a way analogous to the Ex-PRESS device and set in an operationally closed position. The IOP was measured on a regular basis on the operated and control eyes using a rebound tonometer. Once a month the AGDD was adjusted noninvasively from its fully closed to its fully open position and the resulting pressure drop was measured. The contralateral eye was not operated and served as control. After euthanization, the eyes were collected for histology evaluation. The mean preoperative IOP was 11.1 ± 2.4 mm Hg. The IOP was significantly lower for the operated eye (6.8 ± 2 mm Hg) compared to the nonoperated eye (13.1 ± 1.6 mm Hg) during the first 8 days after surgery. When opening the AGDD from its fully closed to fully open position, the IOP dropped significantly from 11.2 ± 2.9 to 4.8 ± 0.9 mm Hg (P < 0.05). Implanting the AGDD is a safe and uncomplicated surgical procedure. The fluidic resistance was noninvasively adjustable during the postoperative period with the AGDD between its fully closed and fully open positions.

Hybridization-induced suppression of coffee ring effect for nucleic acid detection

We demonstrate a method for the detection of nucleic acid using hybridization-induced suppression of the coffee ring effect. When a sessile droplet is pinned on a solid surface, evaporation induces an outward capillary flow that moves suspended particles toward the periphery of the droplet and leaves a ring-shape structure. Compared with spherical particles that are carried to the contact line and form rings, non-spherical particles tend to adhere to each other at the air–water interface where they gain enhanced resistance to the capillary flow and suppress the coffee ring effect. Here, we used suspended microspheres surface-functionalized with single-strand oligonucleotide probes that were complementary to a target DNA. The present target DNA hybridized with the oligonucleotide probe and connected with multiple microspheres, leading to the generation of non-spherical particle agglomerates that resist the capillary flow and form a more uniform deposition of particles after evaporation. Video microscopy and numerical simulation showed that the suppression is because non-spherical particle agglomerates distorted the meniscus surrounding them and exerted a long-range capillary attraction that enhanced the fluidic resistance. Eventually, the microscale hybridization events were translated into the change of coffee ring patterns at macroscale. Using coffee rings as the readout, proof-of-principle studies showed effective sensitivity at low concentrations of 10–100nM with a wide dynamic range from 10−5M to 10−8M, and high specificity that can distinguish the sequence with a single mismatched nucleotide. Owing to the simplicity of the operation and visual readout without the need of a special detector, our approach demonstrates immense potential for the inexpensive and convenient detection of nucleic acid in at resources-limited settings.

Microfluidic perfusion culture chip providing different strengths of shear stress for analysis of vascular endothelial function

We developed a microfluidic perfusion cell culture chip that provides three different shear stress strengths and a large cell culture area for the analysis of vascular endothelial functions. The microfluidic network was composed of shallow flow-control channels of three different depths and deep cell culture channels. The flow-control channels with high fluidic resistances created shear stress strengths ranging from 1.0 to 10.0 dyn/cm(2) in the cell culture channels. The large surface area of the culture channels enabled cultivation of a large number (approximately 6.0 × 10(5)) of cells. We cultured human umbilical vein endothelial cells (HUVECs) and evaluated the changes in cellular morphology and gene expression in response to applied shear stress. The HUVECs were aligned in the direction of flow when exposed to a shear stress of 10.0 dyn/cm(2). Compared with conditions of no shear stress, endothelial nitric oxide synthase mRNA expression increased by 50% and thrombomodulin mRNA expression increased by 8-fold under a shear stress of 9.5 dyn/cm(2).

Glucose Measurement by Affinity Sensor and Pulsed Measurements of Fluidic Resistances: Proof of Principle.

Affinity sensors for glucose are based on a different measuring principle than the commercially available amperometric needle type sensors: reversible affinity interaction of glucose with specific receptors is the primary recognition mechanism instead of an enzymatic glucose oxidation. A novel pulsed-flow micro-fluidic system was used to characterize first the viscosity of a sensitive liquid containing the glucose receptor Concanavalin A and dextran and in a second approach to characterize the geometry of a fluidic resistance. In the viscometric sensor, glucose of the sensitive liquid is equilibrated, while passing through a dialysis chamber, with the surrounding medium. With the membrane flow sensor, the viscosity of the liquid remains constant but the pores of the flow-resisting membrane contain a swellable hydrogel affecting the width of the pores. Two types of hydrogel were tested with the membrane flow sensor; one is highly sensitive to pH and salt concentration, the other contains receptors of phenyl boronic acids to obtain sensitivity to glucose. The viscometric affinity sensor (first approach) showed a linear response over 0 to 30 mmol/L glucose concentration range. The disturbing effect of air bubbles could be compensated for. The sensing proof of principle of the second approach could be demonstrated by its linear response to different saline concentrations; however, the glucose-sensitive membrane developed showed only a small response to glucose. Glucose monitoring based on this pulsed flow measuring principle offers interesting alternatives for the development of CGM systems with different options for the glucose sensing part.

Tuning Fluidic Resistance via Liquid Crystal Microfluidics

Flow of molecularly ordered fluids, like liquid crystals, is inherently coupled with the average local orientation of the molecules, or the director. The anisotropic coupling—typically absent in isotropic fluids—bestows unique functionalities to the flowing matrix. In this work, we harness this anisotropy to pattern different pathways to tunable fluidic resistance within microfluidic devices. We use a nematic liquid crystalline material flowing in microchannels to demonstrate passive and active modulation of the flow resistance. While appropriate surface anchoring conditions—which imprint distinct fluidic resistances within microchannels under similar hydrodynamic parameters—act as passive cues, an external field, e.g., temperature, is used to actively modulate the flow resistance in the microfluidic device. We apply this simple concept to fabricate basic fluidic circuits, which can be hierarchically extended to create complex resistance networks, without any additional design or morphological patterning of the microchannels.

Integrodifferential approaches to frequency analysis and control design for compressible fluid flow in a pipeline element

In this study, modelling, frequency analysis, and optimization of control processes are considered for the fluid flow in pipeline systems. A mathematical model of controlled pipeline elements with distributed parameters is proposed to describe the dynamical behaviour of compressible fluid which is transported in a long rigid tube. By exploiting specific functions representing cross-sectional forces and effective displacements as well as linear approximations of fluidic resistances, the original problem with non-uniform parameters is reduced to a partial differential equation (PDE) system with constant coefficients and homogeneous initial and boundary conditions. Three numerical approaches are applied to an efficient analysis of natural vibrations and reliable control-oriented modelling of pipeline elements. The conventional Galerkin method is compared with the method of integrodifferential relations based on a weak formulation of the constitutive laws. In the latter approach, the original initial-boundary value problem is reduced to the minimization of an error functional which provides explicit energy estimates of the solution quality. A novel projection approach is implemented on the basis of the Petrov–Galerkin method combined with the method of integrodifferential relations. This technique benefits from the advantages of the above-mentioned projection and variational approaches, namely sufficient numerical stability, a lower differential order, and an explicit quality estimation. Numerical optimization procedures, making use of a modified finite element technique, are proposed to obtain a feedforward control strategy for changing the pressure and mass flow inside the pipeline system to a desired operating state. At this given finite point of time, residual elastic oscillations inside the pipeline are minimized. Numerical results, obtained for ideal as well as viscous fluid models, are analysed and discussed.

Label-free viscosity measurement of complex fluids using reversal flow switching manipulation in a microfluidic channel

The accurate viscosity measurement of complex fluids is essential for characterizing fluidic behaviors in blood vessels and in microfluidic channels of lab-on-a-chip devices. A microfluidic platform that accurately identifies biophysical properties of blood can be used as a promising tool for the early detections of cardiovascular and microcirculation diseases. In this study, a flow-switching phenomenon depending on hydrodynamic balancing in a microfluidic channel was adopted to conduct viscosity measurement of complex fluids with label-free operation. A microfluidic device for demonstrating this proposed method was designed to have two inlets for supplying the test and reference fluids, two side channels in parallel, and a junction channel connected to the midpoint of the two side channels. According to this proposed method, viscosities of various fluids with different phases (aqueous, oil, and blood) in relation to that of reference fluid were accurately determined by measuring the switching flow-rate ratio between the test and reference fluids, when a reverse flow of the test or reference fluid occurs in the junction channel. An analytical viscosity formula was derived to measure the viscosity of a test fluid in relation to that of the corresponding reference fluid using a discrete circuit model for the microfluidic device. The experimental analysis for evaluating the effects of various parameters on the performance of the proposed method revealed that the fluidic resistance ratio ( R J L / R L , fluidic resistance in the junction channel ( R J L ) to fluidic resistance in the side channel ( R L )) strongly affects the measurement accuracy. The microfluidic device with smaller R J L / R L values is helpful to measure accurately the viscosity of the test fluid. The proposed method accurately measured the viscosities of various fluids, including single-phase (Glycerin and plasma) and oil-water phase (oil vs. deionized water) fluids, compared with conventional methods. The proposed method was also successfully applied to measure viscosities of blood with varying hematocrits, chemically fixed RBCS, and channel sizes. Based on these experimental results, the proposed method can be effectively used to measure the viscosities of various fluids easily, without any fluorescent labeling and tedious calibration procedures.

A Centrifugal Microfluidics Platform for Potential Application on Immobilization-Free Bead-Based Immunoassays

In this work, we demonstrate a simple yet convenient centrifugal microfluidics, or lab-on-a-disc (LOAD) platform for bead-based immunoassays. The disc contains a network of passive valves for sample manipulation and a bead-aggregating barrier structure to instead of commonly used immobilization method. The narrow-channel structure not only provides a geometric barrier for retaining the beads, but also significantly increased fluidic resistance which results in lower flow rate and longer reaction time for each reagent in the reaction chamber. Centrifuge-forced beads densification in the small junction area and signal concentrating allows high signal sensing capability. The acceleration speed is optimized for largest signal-to-noise ratio. The device uses different rotation speed to trigger a cascade of flow events. The integrated platform contains all the necessary functional elements for conducting one-step parallel assays through a sequential protocol. For our test device, the total time required to complete an immunoassay experiment is typically under 6 minutes. Through this work we have also shown that the use of a geometric barrier for the aggregation of signaling beads is an effective approach for the enhancement of optical signals in common immunoassays. This flexible design is suitable for a broad range of bead-based immunoassays with low-cost and high-speed operation.

Superhydrophobicity-Enabled Interfacial Microfluidics on Textile

ABSTRACTCapillary-driven microfluidics, utilizes the capillary force generated by fibrous hydrophilic materials (e.g., paper and cotton) to drive biological reagents, has been extended to various biological and chemical analyses recently. However, the restricted capillary-driving mechanism persists to be a major challenge for continuous and facilitated biofluidic transport. In this abstract, we have first introduced a new interfacial microfluidic transport principle to automatically and continuously drive three-dimensional liquid flows on a micropatterned superhydrophobic textile (MST). Specifically, the MST platform utilizes the surface tension-induced Laplace pressure to facilitate the liquid motion along the fibers, in addition to the capillary force existing in the fibrous structure. The surface tension-induced pressure can be highly controllable by the sizes of the stitching patterns of hydrophilic yarns and the confined liquid volume. Moreover, the fluidic resistances of various configurations of connecting fibers are quantitatively investigated. Furthermore, a demonstration of the liquid collection ability of MST has been demonstrated on an artificial skin model. The MST can be potentially applied to large volume and continuous biofluidic collection and removal.

Clustering triple microbeads in a dynamic microarray for timing-controllable bead-based reactions

In this study, we developed a dynamic microfluidic device that enables the clustering of three different types of microbeads in a trapping spot and the rearrangement of contacting modes of the clustered microbeads. To achieve these two functions, two features are added to the conventional dynamic microfluidic device. (1) To trap multiple beads, an extended trapping spot with sub-by-pass channels and a valve was employed. (2) To rearrange the clustered microbeads, trapping spots that work only by backward flow were added. The design of the microfluidic device was realized by calculations based on fluidic resistance. By using the designed device, we successfully clustered different types of hydrogel microbeads including target materials, and observed reactions between clustered microbeads. In addition, by rearranging the contacting modes of the clustered microbeads, the reaction could be initiated/terminated at the desired time. We found that this dynamic microfluidic device is applicable to the quantitative analysis of chemical reactions between small amounts of multiple materials.

Design rules and operational optimization for rapid, contamination-free microfluidic transfer using monolithic membrane valves

Abstract Networks of monolithic membrane microvalves integrated into microdevices enable complete automation of liquid-based chemical analyses necessary for fully automated applications, such as spaceflight. Although individual pumping devices and operational routines have been characterized, to date there has been no rigorous evaluation of microvalve layout and its effect on fluidic transfer. Here, we evaluate two microdevices at opposite extremes of fluidic resistance and evaluate three pumping routines on each device. Delay times between operational steps are optimized for fastest fluidic transfer. A 3-valve double-chamber routine enables fastest pumping rates on both devices. On low fluidic resistance devices, a 2-valve (bivalve) pumping routine enables faster fluidic transfer than a 3-valve single-chamber pumping routine. Additionally, low fluidic resistance devices enable significantly faster fluidic transfer (4–6 fold) than their higher resistance counterparts. Back-contamination is qualitatively characterized for the optimized routines; higher fluidic resistance between the pumping architecture and the fluidic output reservoir is the most essential feature for preventing back-contamination. We use these results to suggest design rules to guide future pumping architectures to enable the rapid, contamination-free fluidic transfer that will be necessary in spaceflight applications.

A gel-free multi-well microfluidic device utilizing surface tension for cell culturing

Abstract This paper reports a gel-free multi-well microfluidic chip for cell cultures. Polydimethylsiloxane (PDMS) material was used because of its hydrophobic and gas-permeable features. Surface tension and fluidic channel resistance simplified the procedure of cell injection into the system. The shear stress and the mass-transfer perfusion medium reached a balance through the multi-row square-pillar microstructure and the driven pressure. The cell seeding was completed in 10-mm scaled culture wells in less than 6 s using the microstructure composed of PDMS. The adjustable initial cell density and length of the culture area facilitate its use in desired biological experiments. To verify whether the operation caused cell damage or not, the biological index of supernatants with glutamic oxaloacetic transaminase (GOT) and blood urea nitrogen (BUN) were monitored for 4 days. The 1–4-mm-long multi-rows square-pillar microstructure can sustain HA22T cells for 5 days and still maintain cell viability for up to 90% of seeded cells.

Measurement of microchannel fluidic resistance with a standard voltage meter

A simplified method for measuring the fluidic resistance (Rfluidic) of microfluidic channels is presented, in which the electrical resistance (Relec) of a channel filled with a conductivity standard solution can be measured and directly correlated to Rfluidic using a simple equation. Although a slight correction factor could be applied in this system to improve accuracy, results showed that a standard voltage meter could be used without calibration to determine Rfluidic to within 12% error. Results accurate to within 2% were obtained when a geometric correction factor was applied using these particular channels. When compared to standard flow rate measurements, such as meniscus tracking in outlet tubing, this approach provided a more straightforward alternative and resulted in lower measurement error. The method was validated using 9 different fluidic resistance values (from ∼40 to 600kPasmm−3) and over 30 separately fabricated microfluidic devices. Furthermore, since the method is analogous to resistance measurements with a voltage meter in electrical circuits, dynamic Rfluidic measurements were possible in more complex microfluidic designs. Microchannel Relec was shown to dynamically mimic pressure waveforms applied to a membrane in a variable microfluidic resistor. The variable resistor was then used to dynamically control aqueous-in-oil droplet sizes and spacing, providing a unique and convenient control system for droplet-generating devices. This conductivity-based method for fluidic resistance measurement is thus a useful tool for static or real-time characterization of microfluidic systems.

A pumpless perfusion cell culture cap with two parallel channel layers keeping the flow rate constant

This article presents a novel pumpless perfusion cell culture cap, the gravity-driven flow rate of which is kept constant by the height difference of two parallel channel layers. Previous pumpless perfusion cell culture systems create a gravity-driven flow by means of the hydraulic head difference (Δh) between the source reservoir and the drain reservoir. As more media passes from the source reservoir to the drain reservoir, the source media level decreases and the drain media level increases. Thus, previous works based on a gravity-driven flow were unable to supply a constant flow rate for the perfusion cell culture. However, the proposed perfusion cell culture cap can supply a constant flow rate, because the media level remains unchanged as the media moves laterally through each channel having same media level. In experiments, using the different fluidic resistances, the perfusion cap generated constant flow rates of 871 ± 27 μL h(-1) and 446 ± 11 μL h(-1) . The 871 and 446 μL h(-1) flow rates replace the whole 20 mL medium in the petri dish with a fresh medium for days 1 and 2, respectively. In the perfusion cell (A549 cell line) culture with the 871 μL h(-1) flow rate, the proposed cap can maintain a lactate concentration of about 2200 nmol mL(-1) and an ammonia concentration of about 3200 nmol mL(-1) . Moreover, although the static cell culture maintains cell viability for 5 days, the perfusion cell culture with the 871 μL h(-1) flow rate can maintain cell viability for 9 days.

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.

Hemodialysis Graft Resistance Adjustment Device

Up to eight percent of patients develop steal syndrome after prosthetic dialysis access graft placement, which is characterized by low blood flow to the hand. Steal syndrome results in a cold hand, pain, and in extreme cases, loss of function and tissue damage. A practical and easy way of adjusting the fluidic resistance in a graft to attenuate the risk of steal physiology would greatly benefit both surgeons and patients. This paper describes the design and development of a device that can be attached to a dialysis access graft at the time of surgical implantation to enable providers to externally adjust the resistance of the graft postoperatively. Bench level flow experiments and magnetic setups were used to establish design requirements and test prototypes. The Graft Resistance Adjustment Mechanism (GRAM) can be applied to a standard graft before or after it is implanted and a non-contact magnetic coupling enables actuation through the skin for graft compression. The device features a winch-driven system to provide translational movement for a graft compression unit. We expect such a device to enable noninvasive management of steal syndrome in a manner that does not change the existing graft and support technologies, thus reducing patient complications and reducing costs to hospitals.

Pumpless Fuel Supply Using Pressurized Fuel Regulated by Autonomous Flow-Rate Regulation Valves

A pumpless fuel supply using pressurized fuel with autonomous flow regulation valves is presented. Since micropumps and their control circuitry consume a portion of the electrical power generated in fuel cells, fuel supply without micropumps makes it possible to provide more efficient and inexpensive fuel cells than conventional ones. The flow regulation valves in the present system maintain the constant fuel flow rate from the pressurized fuel chamber even though the fuel pressure decreases. They autonomously adjust fluidic resistance of the channel according to fuel pressure so as to maintain constant flow rate. Compared to previous pumpless fuel supply methods, the present method offers more uniform fuel flow without any fluctuation using a simple structure. The prototypes were fabricated by a polymer micromolding process. In the experimental study using the pressurized deionized water, prototypes with pressure regulation valves showed constant flow rate of 5.38 ± 0.52 μl/s over 80 min and 5.89 ± 0.62 μl/s over 134 min, for the initial pressure in the fuel chamber of 50 and 100 kPa, respectively, while the other prototypes having the same fluidic geometry without flow regulation valves showed higher and gradually decreasing flow rate. The present pumpless fuel supply method providing constant flow rate with autonomous valve operation will be beneficial for the development of next-generation fuel cells.

Single-cell level co-culture platform for intercellular communication

A cell in vivo is part of a large, networked community. An individual cell's fate is strongly influenced by its interactions with neighbouring cells. While this interaction has been recognized as critical in determining cell behaviour, its complexity and heterogeneity has thus far defied characterization by currently available techniques. Herein, we present a single-cell level co-culture platform for studies of dynamic cellular interactions, which is capable of maintaining and tracking single-cell pair interactions to simplify the complexity of intercellular communication. In this platform, heterotypic pairing on a single-cell level is achieved through sequential cell trapping and dynamic variation of fluidic resistance. Individual culture chambers provide trapped cells enough space to migrate and proliferate through multiple generations. Furthermore, the semi-isolated chambers, combined with continuously refreshed medium supplement, allow a stable communication environment around the cells. To demonstrate the platform capability, we cultured and tracked stem cell-fibroblast pairs for several generations. The subsequent effects of cell-cell interactions were then easily observed, due to the addressability of each isolated chamber, and quantitatively characterized. Specifically, we found that paired cells' migration patterns were dependent on their initial distance from each other, and that heterotypic pairing led to distinct proliferation patterns from homotypic, single-cell culture. This study demonstrates the platform utility in providing a detailed and quantitative understanding of the complexity of cellular communication and its effects on cell behaviour in a variety of biological systems.