Microfluidics
Microfluidics refers to a system that manipulates a small amount of fluids using small channels with sizes of ten to hundreds of micrometres. It is a multidisciplinary field that involves molecular analysis, molecular biology, and microelectronics. It has practical applications in the design of systems that process low volumes of fluids to achieve multiplexing, automation, and high-throughput screening. Microfluidics emerged in the beginning of the 1980s and is used in the development of inkjet printheads, DNA chips, lab-on-a-chip technology, micro-propulsion, and micro-thermal technologies.
Typically microfluidic systems transport, mix, separate, or otherwise process fluids. Various applications rely on passive fluid control using capillary forces, in the form of capillary flow modifying elements, akin to flow resistors and flow accelerators. In some applications, external actuation means are additionally used for a directed transport of the media. Examples are rotary drives applying centrifugal forces for the fluid transport on the passive chips. Active microfluidics refers to the defined manipulation of the working fluid by active components such as micropumps or microvalves. Micropumps supply fluids in a continuous manner or are used for dosing. Microvalves determine the flow direction or the mode of movement of pumped liquids. Often, processes normally carried out in a lab are miniaturised on a single chip, which enhances efficiency and mobility, and reduces sample and reagent volumes.
Characteristics
The behaviour of fluids at the microscale can differ from "macrofluidic" behaviour in that factors such as surface tension, energy dissipation, and fluidic resistance start to dominate the system. Microfluidics studies how these behaviours change, and how they can be worked around, or exploited for new uses.At small scales some unintuitive properties appear. In particular, the Reynolds number can become very low. One consequence is co-flowing fluids do not necessarily mix in the traditional sense, as flow becomes laminar rather than turbulent; molecular transport between them must often be through diffusion.
High specificity of chemical and physical properties can also be ensured resulting in more uniform reaction conditions and higher grade products in single and multi-step reactions.
Flow types
Microfluidic flows need only be constrained by geometrical length scale – the modalities and methods used to achieve such a geometrical constraint are highly dependent on the targeted application. Traditionally, microfluidic flows have been generated inside closed channels with the channel cross section being in the order of 10 μm x 10 μm. Each of these methods has its own associated techniques to maintain robust fluid flow which have matured over several years.Open microchannels
The behavior of fluids and their control in open microchannels came into focus around 2005 and applied in air-to-liquid sample collection and chromatography. In open microfluidics, at least one boundary of the system is removed, exposing the fluid to air or another interface. Advantages of open microfluidics include accessibility to the flowing liquid for intervention, larger liquid-gas surface area, and minimized bubble formation. Another advantage of open microfluidics is the ability to integrate open systems with surface-tension driven fluid flow, which eliminates the need for external pumping methods such as peristaltic or syringe pumps. Open microfluidic devices are also easy and inexpensive to fabricate by milling, thermoforming, and hot embossing. In addition, open microfluidics eliminates the need to glue or bond a cover for devices, which could be detrimental to capillary flows. Examples of open microfluidics include open-channel microfluidics, rail-based microfluidics, paper-based, and thread-based microfluidics. Disadvantages to open systems include susceptibility to evaporation, contamination, and limited flow rate.Continuous flow
Continuous flow microfluidics rely on the control of a steady state liquid flow through narrow channels or porous media predominantly by accelerating or hindering fluid flow in capillary elements. In paper based microfluidics, capillary elements can be achieved through the simple variation of section geometry. In general, the actuation of liquid flow is implemented either by external pressure sources, external mechanical pumps, integrated mechanical micropumps, or by combinations of capillary forces and electrokinetic mechanisms. Continuous-flow microfluidic operation is the mainstream approach because it is easy to implement and less sensitive to protein fouling problems. Continuous-flow devices are adequate for many well-defined and simple biochemical applications, and for certain tasks such as chemical separation, but they are less suitable for tasks requiring a high degree of flexibility or fluid manipulations. These closed-channel systems are inherently difficult to integrate and scale because the parameters that govern flow field vary along the flow path making the fluid flow at any one location dependent on the properties of the entire system. Permanently etched microstructures also lead to limited reconfigurability and poor fault tolerance capability.Process monitoring capabilities in continuous-flow systems can be achieved with highly sensitive microfluidic flow sensors based on MEMS technology, which offers resolutions down to the nanoliter range.
Droplet-based
Droplet-based microfluidics is differs from continuous microfluidics; droplet-based microfluidics manipulates discrete volumes of fluids in immiscible phases with low Reynolds number and laminar flow regimes. Interest in droplet-based microfluidics systems has been growing substantially in past decades. Microdroplets allow for handling miniature volumes of fluids conveniently, provide better mixing, encapsulation, sorting, and sensing, and suit high throughput experiments. Exploiting the benefits of droplet-based microfluidics efficiently requires a deep understanding of droplet generation to perform various logical operations such as droplet manipulation, droplet sorting, droplet merging, and droplet breakup.Digital
Alternatives to the above closed-channel continuous-flow systems include novel open structures, where discrete, independently controllable dropletsare manipulated on a substrate using electrowetting. Following the analogy of digital microelectronics, this approach is referred to as digital microfluidics. Le Pesant et al. pioneered the use of electrocapillary forces to move droplets on a digital track. The "fluid transistor" pioneered by Cytonix also played a role. The technology was subsequently commercialised by Duke University. By using discrete unit-volume droplets, a microfluidic function can be reduced to a set of repeated basic operations, i.e., moving one unit of fluid over one unit of distance. This "digitisation" method facilitates the use of a hierarchical and cell-based approach for microfluidic biochip design. Therefore, digital microfluidics offers a flexible and scalable system architecture as well as high fault-tolerance capability. Moreover, because each droplet can be controlled independently, these systems also have dynamic reconfigurability, whereby groups of unit cells in a microfluidic array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. Although droplets are manipulated in confined microfluidic channels, since the control on droplets is not independent, it should not be confused as "digital microfluidics". One common actuation method for digital microfluidics is electrowetting-on-dielectric. Many lab-on-a-chip applications have been demonstrated within the digital microfluidics paradigm using electrowetting.
Paper-based
Paper-based microfluidic devices are proposed to provide portable, cheap, and user-friendly medical diagnostic systems.Paper based microfluidics rely on the phenomenon of capillary penetration in porous media. To tune fluid penetration in porous substrates such as paper in two and three dimensions, the pore structure, wettability and geometry of the microfluidic devices can be controlled while the viscosity and evaporation rate of the liquid play a further significant role. Many such devices feature hydrophobic barriers on hydrophilic paper that passively transport aqueous solutions to outlets where biological reactions take place. Paper-based microfluidics are considered as portable point-of-care biosensors used in a remote setting where advanced medical diagnostic tools are not accessible. Current applications include portable glucose detection and environmental testing, with hopes of reaching areas that lack advanced medical diagnostic tools.
Particle detection
One potential application area involves particle detection in fluids. Particle detection of small fluid-borne particles down to about 1 μm in diameter is typically achieved using a Coulter counter, in which electrical signals are generated when a weakly-conducting fluid such as in saline water is passed through a small pore, so that an electrical signal is generated that is directly proportional to the ratio of the particle volume to the pore volume. The physics behind this is relatively simple, described in a classic paper by DeBlois and Bean, and the implementation first described in Coulter's original patent. This is the method used to e.g. size and count erythrocytes as well as leukocytes for standard blood analysis. The generic term for this method is resistive pulse sensing ; Coulter counting is a trademark term. However, the RPS method does not work well for particles below 1 μm diameter, as the signal-to-noise ratio falls below the reliably detectable limit, set mostly by the size of the pore in which the analyte passes and the input noise of the first-stage amplifier.The limit on the pore size in traditional RPS Coulter counters is set by the method used to make the pores, which while a trade secret, most likely uses traditional mechanical methods. This is where microfluidics can have an impact: The lithography-based production of microfluidic devices, or more likely the production of reusable molds for making microfluidic devices using a molding process, is limited to sizes much smaller than traditional machining. Critical dimensions down to 1 μm are easily fabricated, and with a bit more effort and expense, feature sizes below 100 nm can be patterned reliably as well. This enables the inexpensive production of pores integrated in a microfluidic circuit where the pore diameters can reach sizes of order 100 nm, with a concomitant reduction in the minimum particle diameters by several orders of magnitude.
As a result, there has been some university-based development of microfluidic particle counting and sizing with the accompanying commercialization of this technology. This method has been termed microfluidic resistive pulse sensing.