This paper reviews the latest developments in the design and fabrication of concentration gradient generators for microfluidics-based biological applications. New gradient generator designs and their underlying mass transport principles are discussed. The review provides a blueprint for design considerations of concentration gradients in different applications, specifically biological studies. The paper discusses the basic phenomena associated with microfluidic gradient generation and the different gradient generation modes used in static and dynamic biological assays. Finally, the paper summarizes all factors to consider when using concentration gradient generators and puts forward perspectives on the future development of these devices.

cosmetic and pharmaceutical applications. For dermatological applications, they provide many advantages such as enhanced chemical stability, increased skin hydration effect, and prolonged release (e.g., of perfumes, insect repellents). Cosmetic products containing lipid nanoparticles are already available in the market (Müller et al. 2007;Pardeike et al. 2009). SLN are also an attractive option when used as a drug carrier. It may overcome the problems such as insufficient concentration and poor drug solubility. Advantages also include low toxicity, increased drug stability, high drug load, and precise release control. (Mehnert and Mäder 2001;Almeida and Souto 2007;Belliveau et al. 2012).SLN can be produced through high-pressure homogenization. In this method, the lipid is pushed by high pressure through a narrow gap and accelerated to a high velocity. Large shear stress and cavitation forces will be produced that break the lipid into nanoparticles. This process is energy intensive as the required pressure is up to several hundred bars or even higher. SLN are also prepared by precipitation. The lipid is first dissolved in a solvent. Then, upon either evaporation of the solvent or addition of an anti-solvent, a nanoparticle dispersion will be formed by precipitation of the lipid (Sjöström and Bergenståhl 1992;Dong et al. 2012). Other methods include microemulsion, higher shear homogenization, and ultrasound. More detailed discussion can be found in Mehnert and Mäder (2001).The property of SLN is largely influenced by the size, uniformity, and morphology. Usually, smaller and more uniform SLN are preferred for higher stability, better absorption, and precise release control. In the precipitation synthesis method, one important factor that influences the quality of SLN is the mixing process. The mixing time need to be less than the precipitation time. Otherwise, slow and incomplete mixing will lead to large and wide Abstract The mixing process is critical in the anti-solvent precipitation process of micro-/nanoparticles. It may directly determine the quality of particles, especially the size and uniformity. In this study, a previously developed microfluidic oscillator mixer is used for anti-solvent precipitation of solid lipid (Gelucire 44/14) nanoparticles. This micromixer generates high-frequency oscillatory flow to enhance the fluid mixing. Based on the design, high flow rates of up to 50 ml/min can be achieved to allow relatively high throughput production. Results show that, within a wide concentration range from 10 to 300 mg/ml, solid lipid particles of 50-240 nm can be produced with the polydispersity index ranging from around 0.16 to 0.26. The influences of the anti-solvent to solution flow rate ratio, the geometrical and operating parameters of the oscillator mixer including the secondary chamber depth, and pumping pressure are investigated. For comparison, the same process was also conducted using a static chaotic mixer. Relevant findings provide useful reference for the performance and potential applicatio...

This paper reports design, fabrication and characterization of an air-actuated microvalve and a micropump made of thermoplastic materials. The bonding process was carried out by thermal fusion process with no particular surface treatment. The developed microvalve was used as a reversible switch for controlling both liquid flow and electrical field. Bonding strength of the fabricated microvalves could withstand of liquid and air pressures of up to 600 kPa with no burst failure. The micropump made of three connected microvalves, actuated by compressed air, could generate a liquid flow rate of up to 85 µl/min. The proposed microvalve and micropump can be used as prefabricated off-the-shelf microfluidic functional elements for easy and rapid integration with thermoplastic microfluidic circuitries in a plug-and-play arrangement.

Elucidating the genetic, and neuronal bases for learned behavior is a central problem in neuroscience. A leading system for neurogenetic discovery is the vinegar fly Drosophila melanogaster; fly memory research has identified genes and circuits that mediate aversive and appetitive learning. However, methods to study adaptive food-seeking behavior in this animal have lagged decades behind rodent feeding analysis, largely due to the challenges presented by their small scale. There is currently no method to dynamically control flies' access to food. In rodents, protocols that use dynamic food delivery are a central element of experimental paradigms that date back to the influential work of Skinner. This method is still commonly used in the analysis of learning, memory, addiction, feeding, and many other subjects in experimental psychology. The difficulty of microscale food delivery means this is not a technique used in fly behavior. In the present manuscript we describe a microfluidic chip integrated with machine vision and automation to dynamically control defined liquid food presentations and sensory stimuli. Strikingly, repeated presentations of food at a fixed location produced improvements in path efficiency during food approach. This shows that improved path choice is a learned behavior. Active control of food availability using this microfluidic system is a valuable addition to the methods currently available for the analysis of learned feeding behavior in flies.