Hydrogel Microvalves Research Articles

Control of chemical release in hydrogel microvalve array for localized chemical stimulations

Chemical stimulation is considered as one of the most promising therapeutic solutions for degenerated retina due to its ability to mimic a natural chemical signaling pathway. However, the majority of demonstrated platforms actuate chemicals using bulky external setups. Hence, developing high-resolution chemical release platforms with remote-controlled actuation mechanism is of great interest to the next generation of chemical prosthetics. Moreover, the effectiveness of chemical stimulation depends on several parameters, such as the chemical dosage, pulse duration, and spread radius. Therefore, to engineer the chemical release profile, the actuation mechanism of these localized chemical release platforms needs to be thoroughly studied to facilitate modifications. In this study, we have presented a high-resolution chemical release platform based on a macroporous silicon membrane structure. Chemical release ports defined in the membrane pores can be remotely actuated through thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel with near-infrared (NIR) light. As plasmonic heating elements, gold nanorod (GNR) was incorporated within PNIPAAm hydrogel. The pore size of the hydrogel was tuned by varying tetrahydrofuran content in the hydrogel polymerization solution. We have shown that the chemical release properties through membrane pores can be controlled as required using this approach. This insight can be used to engineer the relevant chemical release parameters, thereby creating an efficient chemical stimulation platform.

Fabrication method and performance of a light-responsive hydrogel microvalve in a microfluidic chip

Microfluidic technology has potential advantages in the complex manipulation of microfluidics on small-sized chips. However, it is difficult to integrate microvalves with complex flow channel structures, and this has limited the miniaturization of microfluidic systems and their portable applications. Light-responsive hydrogel (LRH) materials can rapidly change their volume under laser irradiation and can be used to prepare flexible microvalves to realize the integrated control of microfluidics. A simple fabrication method for an LRH microvalve on a microfluidic chip is proposed. The microspheres, as control elements of the microvalve based on an LRH modified with Laponite RD nanoclay and ferriferous oxide (Fe3O4) nanoparticles, are prepared through a T-shaped flow channel. The microvalve is assembled on the microfluidic chip with a normally closed circulation channel. The open/close performance of the microvalve is represented by the color change of the photonic crystal material. The results show that the LRH microspheres shrink and the flow channel opens after laser irradiation for 2 s. After stopping the laser at 18 s, the valve core swells and the flow channel closes.

On Single and Multiple pH-Sensitive Hydrogel Micro-valves: A 3D Transient Fully Coupled Fluid–Solid Interaction Study

On Single and Multiple pH-Sensitive Hydrogel Micro-valves: A 3D Transient Fully Coupled Fluid–Solid Interaction Study

PH-sensitive hydrogel-based valves: A transient fully-coupled fluid-solid interaction study

pH-sensitive hydrogels are promising materials to be employed in microfluidic devices, especially microvalves. In this paper, a theory of transient swelling of pH-sensitive micro-valve is presented. A transient constitutive model that captures electrical, chemical, and mechanical fields is considered to model the swelling phenomenon. The diffusion of ions into the hydrogel, the electromigration, and convection are described by implementing the Nernst-Planck equation. Assuming Gent model, hydrogel is considered as a compressible hyperelastic material and osmotic pressure is assumed as an external loading. Due to benefits of in-plane valves, a design of the micro-valve is studied. Design simplicity and great sealing are vital factors which can be considered as an advantage of this valve for fabrication. This design and modeling approach has not been used for pH-sensitive hydrogels in earlier works. Thus, we have studied the transient swelling of pH-sensitive hydrogel microvalve, when effects of fluid-structure-interaction are examined on valve performance. It is noted that in most previous studies, equilibrium conditions have been assumed. While considering transient fully-coupled fluid-structure-interaction is necessary to capture a more realistic modeling. The results illustrate that the microvalve blocks the channel much earlier than reaching the equilibrium-state, which implies importance of the transient behavior of hydrogels.

Study of Fluid–Structure Interaction in a Functionally Graded pH-Sensitive Hydrogel Micro-Valve

In this work, fluid–structure interaction (FSI) simulations, as well as non-FSI ones, are conducted to study the behavior of a functionally graded (FG) pH-sensitive micro-valve. The FEM analysis of the hydrogel is performed in ABAQUS while the fluid domain is analyzed in ANSYS fluent. To investigate the FSI and FG effects, both FSI and non-FSI simulations are performed for pH-sensitive micro-valve with homogeneous cross-linking distribution beside the FG cases. Two simulation domains are coupled by using a third-party software named MpCCI for both FSI and non-FSI simulations. For the FG hydrogel, linear and exponential property distributions are considered. The obtained results show a significant difference between the FG and homogeneous hydrogel behavior for both simulation methods. Additionally, the results emphasize that FSI consideration has a crucial role in the design of these smart devices. Especially, remarkable difference is observed for the closing pH of the micro-valve as well as the flow-rate diagrams. For example, a leakage is observed in FSI simulations for the closing pH of the non-FSI simulations that indicates the importance of the FSI effect. Finally, the effect of the cross-linking density distribution and the inlet pressure of micro-valve are studied and the results are analyzed.

Analysis of temperature-sensitive hydrogel microvalves in a T-junction flow sorter using full scale fluid–structure interaction

Hydrogels have attracted attention in microfluidic applications as sensors and actuators due to their ability to undergo huge volume changes when subjected to environmental stimuli. In this study, a T-junction flow sorter is numerically investigated. Each of the branches involves one hydrogel microvalve with reverse sensitivity to temperature changes. The valve’s functionality is studied with and without considering fluid–structure interaction for various inlet pressures. The results of fluid–structure interaction and non-fluid–structure interaction solutions, such as fluid flow rate and valves close temperature, are presented and compared. In order to reduce hydrogel’s response time, the solution is employed for multiple valves patterns. It can be concluded that the hydrogel deformation due to the fluid pressure has a significant effect on the valves’ operational parameters which cannot be ignored in design and analysis.

Design and fluid-structure interaction analysis for a microfluidic T-junction with chemo-responsive hydrogel valves

Due to the deformation ability even under small loads, hydrogels have been widely used as a type of soft materials in various applications such as actuating and sensing, and have attracted many researchers to study their behaviors. In this paper, the behavior of hydrogel micro-valves with reverse sensitivity to the pH inside a T-junction flow sorter is investigated. With the fluid-structure interaction (FSI) approach, the effects of various parameters such as the inlet pressure and the pH value on the stress and deformation of the micro-valves are examined, and the results with and without FSI, including the flow rate and the closure pH, are compared. In order to reduce the response time of hydrogels, the effects of three different patterns on the performance of the micro-valves are explored. Eventually, it is concluded that FSI is a key influential factor in designing and analyzing the behaviors of hydrogels.

Hydrogel Microvalves as Control Elements for Parallelized Enzymatic Cascade Reactions in Microfluidics.

Compartmentalized microfluidic devices with immobilized catalysts are a valuable tool for overcoming the incompatibility challenge in (bio) catalytic cascade reactions and high-throughput screening of multiple reaction parameters. To achieve flow control in microfluidics, stimuli-responsive hydrogel microvalves were previously introduced. However, an application of this valve concept for the control of multistep reactions was not yet shown. To fill this gap, we show the integration of thermoresponsive poly(N-isopropylacrylamide) (PNiPAAm) microvalves (diameter: 500 and 600 µm) into PDMS-on-glass microfluidic devices for the control of parallelized enzyme-catalyzed cascade reactions. As a proof-of-principle, the biocatalysts glucose oxidase (GOx), horseradish peroxidase (HRP) and myoglobin (Myo) were immobilized in photopatterned hydrogel dot arrays (diameter of the dots: 350 µm, amount of enzymes: 0.13–2.3 µg) within three compartments of the device. Switching of the microvalves was achieved within 4 to 6 s and thereby the fluid pathway of the enzyme substrate solution (5 mmol/L) in the device was determined. Consequently, either the enzyme cascade reaction GOx-HRP or GOx-Myo was performed and continuously quantified by ultraviolet-visible (UV-Vis) spectroscopy. The functionality of the microvalves was shown in four hourly switching cycles and visualized by the path-dependent substrate conversion.

Behavior of a smart one-way micro-valve considering fluid–structure interaction

Smart hydrogels are soft materials which can be applied in sensors and actuators especially in microfluidics in which the fluid–structure interaction is important. In this work, first, the behavior of a one-way hydrogel micro-valve is investigated by considering the fluid–structure interaction effect for a specified geometry of the micro-valve. Second, both the fluid–structure interaction and non-fluid–structure interaction simulations are conducted to study the fluid flow effect on the operational parameters of the micro-valve. The obtained results show that the fluid–structure interaction effects are important and have a considerable influence on the micro-valve parameters especially on its closing temperature. Thereafter, a precise study on the micro-valve is executed by considering the micro-valve operational parameters such as inlet pressure, head size, crosslinking density, and breaking pressure at different temperatures. The results show the importance of considering the fluid–structure interaction effect in the design of these devices.

Modeling the closing behavior of a smart hydrogel micro-valve

Smart hydrogel micro-valves are essential components of micro-chemo-mechanical fluid systems. These valves are based on phase-changeable polymers. They can open and close micro-fluidic channels depending on the chemical concentration or the temperature in the fluid. A concept of finite element–based modeling in combination with network methods to simulate concentration-triggered, phase-changeable hydrogels is proposed. We introduce a temperature domain as a replication domain to substitute insufficiently implemented domains. With the used simulation tools, problems are highlighted and their solutions are presented. The computed parameters of such valves are included in a circuit representation, which is capable of efficiently computing large-scale micro-fluidic systems. These methods will help predict, visualize, and understand polymeric swelling behavior as well as the performance of large-scale chip applications before any complex experiment is performed.

A Combined Analytical–Numerical Investigation on Photosensitive Hydrogel Micro-Valves

In this paper, employing photo-thermal sensitive (PTS) hydrogels, a photosensitive bio-compatible micro-valve is investigated. In this regard, the energy representation and governing equations of PTS hydrogels are described. Two benchmark problems common in micro-fluidic designs are solved using the presented theory, and the deformation and stress distributions are calculated. The theory is implemented into a finite element (FE) framework by developing a user-defined subroutine. To properly validate the FE model, the FE results are compared with the proposed analytical results. The confirmed numerical method is then employed to investigate two different realistic micro-valve structures. The constructions are composed of three jacket-pillar structures arranged in two different patterns. In this step, the nonlinear contact between the components of structures and presumptive rigid walls are added to the thermo-mechanical deformation of the photosensitive micro-jackets. The contact length and contact pressure are investigated. By calculating all necessary mechanical parameters, the analysis results can be utilized in the design procedure of a photosensitive micro-valve and pave the way for the industrial production of the next generation micro-fluidic devices.

Multiphysics equivalent circuit of a thermally controlled hydrogel microvalve

Temperature-responsive hydrogels are polymer particles whose equilibrium size depends on the temperature of the water they are immersed in. Here we present an equivalent circuit model of a temperature-controlled microvalve based on hydrogel particles. The resulting network model consists of three physical subsystems. The thermal subsystem considers the heat capacities and thermal resistances of the layers of the valve and the coupling to the ambient environment. The polymeric subsystem describes the relaxation of the hydrogel particles to the temperature-dependent equilibrium size. The fluidic subsystem consists of the supply channel and a chamber whose cross section varies according to the size of the hydrogel particles. All subsystems are described and coupled within one single circuit. Thus the transient behavior of the valve can be calculated using a circuit simulator. Simulation results for a setup are presented and compared with experiments.

A simple strategy for in situ fabrication of a smart hydrogel microvalve within microchannels for thermostatic control.

Self-regulation of temperature in microchip systems is crucial for their applications in biomedical fields such as cell culture and biomolecule synthesis as well as those cases that require constant temperature conditions. Here we report on a simple and versatile approach for in situ fabrication of a smart hydrogel microvalve within a microchip for thermostatic control. The thermo-responsive hydrogel microvalve enables the "on-off" switch by sensing temperature fluctuations to control the fluid flux as well as the fluid heat exchange for self-regulation of the temperature at a constant range. Such temperature self-regulation is demonstrated by integrating the microvalve-incorporated microchip into the flow circulation loop of a micro-heat-exchanging system for thermostatic control. Moreover, the microvalve-incorporated microchip is employed for culturing cells under temperature self-regulation. The smart microvalve shows great potential as a temperature controller for applications that require thermostatic conditions. This approach offers a facile and flexible strategy for in situ fabricating hydrogel microvalves within microchips as chemostats and microreactors for biomedical applications.

Fabrication of an optically driven pH gradient generator based on self-assembled proton pumps

Optically manipulating the local pH of a target solution in a microchannel, or reservoir, provides a mechanism for activating and controlling a variety of biological and chemical processes on Lab-on-a-Chip (LOC) devices and micro-total analysis systems (μ-TAS). A microscale pH gradient generator that exploits the light-activated molecular proton pumps found in the purple membranes (PM) of bacteriorhodopsin is described in this paper. The photo-electro-chemical transducer is an ultrathin layer (~13 nm) of oriented PM patches self-assembled on an Au-coated porous substrate. A biotin labeling and streptavidin molecular recognition technique is used to ensure that the extracellular side of all PM patches is attached to the porous substrate enabling unidirectional and efficient transport of ions across the transducer surface. The photo-induced proton pumps generate a flow of ions that produce a measurable change in pH between the separated solutions. The self-assembly procedure is experimentally quantified based on the capacitance characteristics of the bR membranes. The investigation confirms that the transducer is covered with the bR proton pumps at a mass density of 2.33 ng/cm2. Experimental tests also show that the proposed transducer can repeatedly generate pH gradients as high as 0.42 and absolute voltage differences as high as 25 mV when illuminated by an 18 mW, 568 nm light source. Furthermore, the ΔpH is observed to be nonlinear with respect to light intensity and exposure time. The ΔpH of the target solution is sufficient to cause a phenolphthalein indicator dye to change color or an ionic hydrogel micro-valve to expand.

Implantable drug delivery device using frequency-controlled wireless hydrogel microvalves

This paper reports a micromachined drug delivery device that is wirelessly operated using radiofrequency magnetic fields for implant applications. The controlled release from the drug reservoir of the device is achieved with the microvalves of poly(N-isopropylacrylamide) thermoresponsive hydrogel that are actuated with a wireless resonant heater, which is activated only when the field frequency is tuned to the resonant frequency of the heater circuit. The device is constructed by bonding a 1-mm-thick polyimide component with the reservoir cavity to the heater circuit that uses a planar coil with the size of 5-10mm fabricated on polyimide film, making all the outer surfaces to be polyimide. The release holes created in a reservoir wall are opened/closed by the hydrogel microvalves that are formed inside the reservoir by in-situ photolithography that uses the reservoir wall as a photomask, providing the hydrogel structures self-aligned to the release holes. The wireless heaters exhibit fast and strong response to the field frequency, with a temperature increase of up to 20°C for the heater that has the 34-MHz resonant frequency, achieving 38-% shrinkage of swelled hydrogel when the heater is excited at its resonance. An active frequency range of ~2MHz is observed for the hydrogel actuation. Detailed characteristics in the fabrication and actuation of the hydrogel microvalves as well as experimental demonstrations of frequency-controlled temporal release are reported.

Thermoresponsive Hydrogel Microvalve Based on Magnetic Nanoheaters for Microfluidics

AbstractA novel magneto-active gel based nanomaterial system is presented as an externally tunable flow controller inside a microfluidic channel using the thermoresponsive property of the structure. Integration of ferromagnetic nanoparticles (Fe3O4) in the temperature sensitive polymer-poly (N-isopropylacrylamide) (PNIPAM) provides the swelling and de-swelling behavior of magnetic stimuli controlled micro-component by generating the heat due to the hysteresis loss of Fe3o4 under exposure in an alternating magnetic field. The shrinkage rates of the nanomaterial system at the bulk and micro scale are investigated. Size dependent shrinkage rate and actuation efficiency are ideal for various applications like magnetic micro/nano pump, magnetic field controlled drug delivery devices and magnetic switch applications.

The microscopy cell (MicCell), a versatile modular flowthrough system for cell biology, biomaterial research, and nanotechnology

We describe a novel microfluidic perfusion system for high-resolution microscopes. Its modular design allows pre-coating of the coverslip surface with reagents, biomolecules, or cells. A poly(dimethylsiloxane) (PDMS) layer is cast in a special molding station, using masters made by photolithography and dry etching of silicon or by photoresist patterning on glass or silicon. This channel system can be reused while the coverslip is exchanged between experiments. As normal fluidic connectors are used, the link to external, computer-programmable syringe pumps is standardized and various fluidic channel networks can be used in the same setup. The system can house hydrogel microvalves and microelectrodes close to the imaging area to control the influx of reaction partners. We present a range of applications, including single-molecule analysis by fluorescence correlation spectroscopy (FCS), manipulation of single molecules for nanostructuring by hydrodynamic flow fields or the action of motor proteins, generation of concentration gradients, trapping and stretching of live cells using optical fibers precisely mounted in the PDMS layer, and the integration of microelectrodes for actuation and sensing.