![]() ![]() As a multi-purpose concentration gradient maker, it has four independent inlets. In this work, we describe a device fabricated by soft lithography and consisting of a Christmas-tree network. Thus, it may be necessary to redesign a footprint if applied to new occasions. The concentration distribution profile within the channel is determined by the length of the channel, the splitting ratio of the fluids, and also the numbers of inlets and outlets. They have been widely studied in various fields in recent decades. Microfluidic concentration gradient generators are among the most efficient devices employed for precise generation of various concentration gradients. By the combination control of flow rate and chip geometries, an automated drug dilution platform was presented recently. Another principle of structure-based mixing or concentration gradient makers is topological mixing schemes, which split, rotate, and recombine the microflows to perform efficient mixing by diffusion. By varying the lengths of microchannel, the volume of dispensed sample solutions was dictated, and then complex gradient profiles were generated. One more example, a structure-based approach, was presented to generate linear or nonlinear chemical gradients. In this work, it was shown that the concentration gradient profile could be controlled not only by the dynamic inputs but also by channel geometries. This approach has been successfully used to mix many kinds of microfluids. ![]() In addition, a systematic investigation was carried out to demonstrate the universal approach to generate stable gradients of any profiles by experimental and mathematical methods. By using this device, linear gradients with dynamically controlled characteristics (i.e., slope, baseline, or direction of the line), and nonlinear gradients with controlled nonlinearity were illustrated. Then, another impressive device was developed to generate dynamic temporal and spatial concentration gradients using one single microfluidic device. One of the earliest designs was a design for controlled diffusive mixing of reagents, which generated a range of shapes for the gradients, such as linear, parabolic, and periodic. To address a nonlinear concentration gradient profile, a range of different microfluidic mixing technologies have been developed. Generally speaking, a linear concentration gradient generator can be easily set up by classic Christmas-tree microfluidic channel networks, convection-driven flow, or novel designs such as centrifugal microfluidics or 3D-printing stereo networks. Past research studies have shown that a device that can generate spatially and temporally controlled gradients is regarded as a robust and powerful method to investigate migratory cells, drug screening, oil production screening from microalgae, nucleation and growth of crystals, and wound healing under a variety of conditions. In fact, the ability to generate stable linear or nonlinear spatial chemical gradient profiles within microfluidics has been adapted extensively for analysis. With the help of external resources, such as electric signals, magnetic fields, acoustic energy, or light sources, microfluids can be mixed efficiently. Most biological or chemical samples are composed of a mixture of several kinds of reagents, and thus on-chip mixing is an essential step in many applications. With their advantages of low reagent consumption, large integration in small footprints, near-zero dead volume, and low-cost fabrications, polydimethylsiloxane (PDMS) microfluidic devices are increasing used for lab-on-a-chip applications. With on-demand flow rate ratios, the FFRR microfluidic device could be used for many lab-on-a-chip applications where flexible concentration profiles are required for analysis. Its performance was analyzed using numerical simulation models and experimental investigations, and it showed an excellent time response (~10 s). To demonstrate the advantages of this approach, we used a Christmas-tree-like microfluidic chip as the demo. Here, we present an FFRR (feed flow rate ratio) adjustment approach to generate tens of types of concentration gradient profiles with one single device. To address this challenge, we developed a soft-lithography-fabricated microfluidic platform that enabled one single device to be used as a concentration maker, which could generate linear, bell-type, or even S-type concentration profiles by tuning the feed flow rate ratios of each independent inlet. These microfluidic devices have untapped potential for varying concentration patterns by the use of one single device or by easy-to-operate procedures. Microfluidic chips-in which chemical or biological fluid samples are mixed into linear or nonlinear concentration distribution profiles-have generated enormous enthusiasm of their ability to develop patterns for drug release and their potential toxicology applications. ![]()
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