Where the moment of testing is the essence of what happens on a lab-on-a-chip, flow control is the infrastructure that makes the test work. Flow control elements are the ‘traffic controllers’ of the microfluidic highway. For a test on a microfluidic platform to be successful, it is of vital importance that the used liquids are in the right place at the right time. In-depth knowledge of both the fluid’s and the material’s behavior is critical to make use of flow control technologies in the right way.
Are you in the process of developing a biomedical test platform? Then you have a clear view of what you want to achieve. You know which test you want to run and which samples and reagents to use. Are you struggling with the infrastructure and layout of the platform? Keep on reading! In this article, our flow control expert Fabien Abeille, Senior R&D Scientist, explains the process of determining the most suitable flow control measures. With the right advice, you can solve the puzzle and make sure you have the best solution for your application.
Fabien: ‘When we sit down with a customer to discuss flow control choices for a consumable, we usually start by defining if we should consider a pneumatically driven or other active approach, a more capillary/passive one or a combination of both. Active flow control relies on an external input for actuation. In passive flow control, the movement is intrinsic and determined by the geometry and the capillary properties of the channels.’
How do we weigh the choice between active or passive flow? When discussing these options, the following three aspects are always addressed:
The amount of liquid that has to be processed is a very important factor. With active flow control, we usually have to deal with somewhat larger feature sizes in comparison to passive flow control devices, which makes them less suitable for very small sample volumes (< 1 microliter). In cases where only a few microliters are available as input (costly reagent, minimal sampling from patient), the capillary approach is typically more suitable.
Many applications may require handling larger volumes however. For instance, when a sample contains low concentrations of analytes or targets to extract, one may need to process relatively large volumes (a few hundreds of microliters) to ensure that enough of these analytes/targets can be captured and quantified. In these cases, it makes sense to opt for an active flow control system.
The typical flow rate in a capillary device would generally not exceed a few microliter/min while faster flow rates (1-2 orders of magnitude higher) can be easily achieved with active flow control. If the volumes to be processed are significant, it would be better to rely on a flow control able to process such a volume in a relatively short time. Certainly, in the case of diagnostics, results are usually expected on a short time scale.
In some cell culture applications, one may want to induce specific shear rates to stimulate cells for example. This requires relatively high flow rates that are typically only achievable when using active flow control systems.
Besides, capillary systems are not meant to work for hours since drying may be a challenge, and also their network can hardly be reused to repeat operations (see next point).
Active flow control can offer repetitive actuation that capillary systems cannot: they are single actuated. A pneumatic valve can be actuated over and over and still be functional. In this way, the same fluidic network can be reused to repeat fluidic operations or to process various samples consecutively. For a capillary valve or system, that would not be the case, or at least its reliability would be very variable and uncertain. The reason for this is that capillary systems are susceptible to surface states/conditions. Once a capillary valve is triggered, one would necessarily need to wait until it has dried before hoping it to work again. Because liquids flowing through that valve transport various components (salts, biomolecules, etc. ...), these will be left at the valve after drying, modifying the surface of the valve thus impacting greatly on its performance for subsequent use.
The most suitable method of flow control is determined on the basis of these three elements: volumes, flow rates and reusability. However, there are other factors that have to be considered, such as the choice of the material that is used. This will be determined on which material fits best in the context the customer wants to use the chip. Due to the disposable nature of many biomedical test platforms, low-cost materials, such as polymers, are often used.
At Micronit, we have established processes that use polystyrene (PS) and cyclic olefin copolymer (COC) as substrate materials for consumables that integrate flow control functionalities. However, specific cases might require the use of other materials, such as polycarbonate (PC) or poly-methylmethacrylate (PMMA). The choice of the material is not a trivial endeavor. Many factors need to be considered, for example chemical resistance, optical properties (transparency, autofluorescence), permeability to gas/water, thermal properties, medical-grade compliance, specialized lab vs. on-site use, etc. Some of the flow control technologies can be translated easily to any of these materials, while others may require some more development.
It is also possible that the flow control elements have to be integrated on a platform made of various materials. Such hybrid solutions must be discussed in good time in order to result in a properly functioning product. To this end, we go through a phased product development process with customers. Read more about this at https://www.micronit.com/working-together/from-idea-to-product/product-development.
As you can see, essential decisions have to be made at an early stage in the development process, because they will determine the entire further layout of the product. Contact an expert in time to discuss these choices!
Would you like more specific information about the principles of the different flow control elements in polymer? Then read our white paper on this topic. Download it right away!