Stimuli‐sensitive hydrogels have an outstanding potential for miniaturized, integrated sensor, and actuator systems and especially for lab‐on‐chip technology, but the application is still in its infancy. One major reason may be that design and realization of hydrogel‐based systems are exceptionally complex and demanding. Here, the design parameters of a key component, the hydrogel‐based valve, are discussed in their entirety. Key developments in the fields of stimuli‐sensitive hydrogels are highlighted and the necessary know‐how in material behavior, microstructuring technologies, modeling and name five essential design guidelines as well as scaling laws for hydrogel‐based components, including microfluidic one‐directional valves, microelectromechanical systems valves, self‐regulating, chemomechanical valves, and chemofluidic transistors, is provided.

We present a technique for the simultaneous photostructuring of hydrogels on the μm scale with different compositions on one substrate. The existing methods (e.g. spin-coating of the hydrogel precursor and application of simple moulds or spacers) have less potential to integrate spatially separated functional hydrogel dots as needed for the fabrication of complex polydimethylsiloxane (PDMS) on-glass microfluidic chips. Here, we report a method for the fast production of precisely placed hydrogel structures with adjustable height (≤80 μm) and width (≤500 μm) on glass substrates utilizing black polyoxymethylene moulds. The integration of several chambers for different hydrogel precursor solutions in one mould allows the simultaneous photopolymerization of hydrogels with different compositions. To visualize the difference in composition of the hydrogel dots and to demonstrate the precision in structuring, various quantum dots were added to the hydrogel precursor solutions and physically entrapped during the photopolymerization. To show the high potential of our photostructuring method, a microfluidic double-chamber reactor was designed and the variability in the performance of tri-enzymatic cascade reactions with optionally spatially separated or non-separated enzymes β-galactosidase, glucose oxidase, and horseradish peroxidase was visualized.

The interest in large-scale integrated (LSI) microfluidic systems that perform high-throughput biological and chemical laboratory investigations on a single chip is steadily growing. Such highly integrated Labs-on-a-Chip (LoC) provide fast analysis, high functionality, outstanding reproducibility at low cost per sample, and small demand of reagents. One LoC platform technology capable of LSI relies on specific intrinsically active polymers, the so-called stimuli-responsive hydrogels. Analogous to microelectronics, the active components of the chips can be realized by photolithographic micro-patterning of functional layers. The miniaturization potential and the integration degree of the microfluidic circuits depend on the capability of the photolithographic process to pattern hydrogel layers with high resolution, and they typically require expensive cleanroom equipment. Here, we propose, compare, and discuss a cost-efficient do-it-yourself (DIY) photolithographic set-up suitable to micro-pattern hydrogel-layers with a resolution as needed for very large-scale integrated (VLSI) microfluidics. The achievable structure dimensions are in the lower micrometer scale, down to a feature size of 20 µm with aspect ratios of 1:5 and maximum integration densities of 20,000 hydrogel patterns per cm². Furthermore, we demonstrate the effects of miniaturization on the efficiency of a hydrogel-based microreactor system by increasing the surface area to volume (SA:V) ratio of integrated bioactive hydrogels. We then determine and discuss a correlation between ultraviolet (UV) exposure time, cross-linking density of polymers, and the degree of immobilization of bioactive components.

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.

Despite great progress of lab‐on‐a‐chip (LoC) technology platforms in the last 30 years, there is a lack of standardized microfluidic components, real on‐chip automation and progressive functional scalability of the fluidic circuits. Hydrogel‐based microfluidic circuits have a high scaling potential and provide on‐chip automation, but are complex in system design. An advanced circuit concept for planar microfluidic chip architectures, originating from the early era of the semiconductor‐based resistor‐transistor‐logic (RTL) is presented and the hydrogel‐based chemical volume phase transition transistor (CVPT) for logic gate operations is implemented. The circuit concept (CVPT‐RTL) is robust and simple in design, feasible with common materials and manufacturing techniques of the LoC technology. Thereby, three major challenges are solved: contamination issues, maintaining the signal compliance for cascadability, and chemical signal inversion. As a central element, a CVPT cascode is introduced. The functionality of the concept is verified by a 24 h test of the NAND gate operation and a self‐automated chemofluidic analog‐to‐digital converter, utilized as interface between bioreactors and extended microfluidic logic circuits. Moreover, the CVPT‐RTL cascode demonstrates the expected self‐stabilizing performance of the NAND gate. Accompanying simulations of the component behavior based on a network description implemented in Matlab Simscape match with the experimental results.