Microfluidic sample transport
In order to initiate, maintain and control flow through a microchannel network a number of functional elements are necessary, such as valves and rectifiers, pumps or pump mechanisms, and injection or dispensing units. Additionally, flow selectors and flow focusing functionalities as well as mixers might be present in some microfluidic systems as well.
Authored by: Jörg Kutter DANMARKS TEKNISKE UNIVERSITET
Microfluidics entails the ability to manipulate and control flows of liquids and gases in micrometer-sized conduits. Most microfluidic flow happens in the low Reynolds number (non-turbulent) regime, with well-defined flowlines, where mass transport between adjacent laminae is by diffusion only. (see more on microfluidics basics here)
Valves allow to control the passage of fluids (flow or no flow), determine the direction of flow (flow rectification), and can help to adjust the magnitude of the established flow. Not all of the many developed valves for microfluidics offer all of the above mentioned functionalities at the same time.
An ideal valve (to be incorporated into microfluidic systems) can be said to display the following characteristics:
- zero leakage (when in its closed state, no flow gets through the valve)
- zero power consumption (ideally, no energy is necessary to switch between the open and closed state, or to maintain one of the states)
- zero dead volume (the valve does not introduce unnecessary extra volumes)
- zero response time (the transition from one state to another is as fast as possible)
- infinite differential pressure capability (this is typically for passive valves (see below): just above the threshold pressure opens the valve completely, just below the threshold pressure closes the valve completely)
- potential for linear operation (the possibility to open up a bit, then a bit more and so on in order to control the flow magnitude; this characteristic is, obviously, not compatible with the infinite pressure capability mentioned above)
- insensitivity to particulate contamination (valve designs should accommodate for the possibility to operate even when particulate contaminants can make leak-free closing of valves difficult)
- ability to operate with fluids of any density, viscosity and chemistry
A wealth of designs exists for microfluidic valves; however, none of them is able to fulfill all the mentioned ideal requirements. A classification attempt for microfluidic valves distinguishes between active and passive valves. Passive valves operate without the need for external energy sources, but instead exploit energies already present in the system (often, pressure differentials). Active valves, on the other hand, require external energy, and an actuation principle where the external energy is transducted to typically a mechanical action that either restricts or opens for the passage of fluids.
Passive valves (also called check valves) are often of the cantilever, flap or lid variety (not unlike the valves in the human heart), and function by mechanical displacement on account of a sufficient overpressure upstream of the valve. The same displacement is, however, not possible in the opposite direction, thus performing the basic function of a valve. Another important group of passive valves are the so-called burst valves, which only work once. They stop flow because of a restriction in the channel dimensions (increased flow resistance) or at a patch of chemically modified channel surface (increased surface tension). Only if sufficient pressure is applied will these valves “break” or “burst” and allow flow to resume.
Active valves exploit, for example, the volume expansion of a working fluid that is in a closed compartment and then electrically heated (thermopneumatic actuation). The expansion is used to mechanically deflect part of the valve, which will then seal off flow until the current is switched off and the working fluid cools down again. Due to the small dimensions of microfluidic valves and the good heat transport in such system, switching times of these valves are sufficiently fast. Freeze-thaw valves directly use the liquid present in the microchannel, which is locally frozen, thus shutting off flow. Another, often used example of active valves are found in microfluidic systems made from an elastomeric polymer, such as silicone rubber. Here, the elastic fluid-carrying channel is “squashed” shut where it crosses over an air-pressurized control channel - this is entirely equivalent to stepping on a garden hose to prevent flow. Clever “wiring” of working channels and control channels allows complex fluidic protocols to be realized using these types of valves.
In order to move fluids through the microfluidic channel network either external energy sources (pressurized air containers), simple physical principles (capillary action, gravity, surface tension, electroosmosis) or truly integrated miniaturized pumps are employed.
When choosing a particular pumping solution for a microfluidic system the following represents a typical “wishlist”:
- as little flow rate pulsation as possible
- flow rate adjustable over a certain range
- operation under varying counterpressure situations
- flow rate insensitive to counterpressures
- resistant to aggressive chemicals, works for long periods of time, also at higher temperatures
- production costs (material, fabrication, assembly) as low as possible
Simpler pumping schemes (e.g. by exploiting capillary forces) may only allow limited control of the flow rate, but are often easier to implement and amenable to mass production. More complicated integrated micropumps built by invoking elaborate microfabrication strategies can offer more operational freedom, but should, on account of their high production costs, not be integrated in, for example, microfluidic systems intended for a one-time use in medical applications.
One classification attempt for microfluidic pumps and pumping schemes distinguishes between valveless pumps and pumps, which need valves. Most MEMS-type micropumps include a pump chamber, where the volume is periodically altered by a mechanical action, and which therefore require valves to rectify the flow and get an overall net flow in one direction. The actuation of the pump chamber is often based on similar principles as used for active valves. Valveless pumps reduce the amount of actuators and moving parts, which can be prone to mechanical fatigue, and instead use particular microfluidic elements, so-called diffusor-nozzle pairs to rectify flow. These elements display a different fluidic resistance in the two possible flow directions and thus establish a preferred flow direction (albeit with residual leak flow in the opposite direction).
An important and popular pumping mechanism in microfluidic systems exploits the phenomenon of electroosmosis. The advantage here is that the engineering effort to realize this type of pumping is fairly moderate and pumping is easily established. However, the flow is inherently dependent on the chemistry in the system (composition of the liquid and material of the channel walls) and thus often very hard to control.
Also of importance is the use of centrifugal forces to push liquids through channel networks. Typically, the channels are established on a circular substrate, which can be spun to force liquids from the center of the disk to its perimeter. Careful channel design and the use of burst valves allows sufficient fluidic control to perform most relevant operations.
Other microfluidic elements:
Many microfluidic applications require definition of specific fluidic volumes for further processing. Injectors and dispensers take care of this task. Injectors often use particular channel designs or involve valves for the definition of a volume of one liquid into a continuous stream of another liquid. Similar setups are used for generation of droplets or slugs in two-phase microfluidics. Dispensers, on the other hand, typically dispense certain liquid volumes into or through air and/or onto solid surfaces (see also the article on liquid handling for further details).
Because of the predominantly occurring low Reynolds number flow in microfluidic systems, it is straightforward to combine different fluidic streams into one channel, thus forming laminae flowing alongside each other downstream. Mass transport perpendicular to the main flow direction only occurs by diffusion. Formation of laminae can be used for flow focusing, by increasing the flowrates of two flanking streams with respect to a center stream, thus narrowing down the width of that center stream. Alternatively, changing the flowrates of the flanking streams in a non-symmetrical fashion allows to position the center stream at different lateral positions of the channel, thus making it possible to guide the center stream into different outlet channels. This is the function of a flow selector.
Finally, an important functional element for microfluidics are mixers or mixing structures. Because of the predominance of non-turbulent flow, diffusion is the only available transport mechanism to induce mixing between two previously joined fluidic laminae. As a consequence of the Einstein-Schmoluchowski relation between diffusion pathlength and diffusion time, many mixer designs seek to minimize the necessary diffusion pathlengths, e.g., by splitting and re-laminating. Other strategies attempt to stretch and fold the laminae, again in order to minimize diffusion pathlengths. Finally, active mixers use external energy to create (chaotic) advection to accelerate the mixing process.
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