Mixing at the microscale: essential and challenging
Microfluidic devices have wide applicability in biomedical research, clinical diagnostics, and drug development. However, a primary limitation of microfluidic systems is their inability to achieve thorough and rapid mixing. Mixing is essential for achieving rapid reactions and reliable results. Microfluidic systems, are typically low Reynold’s number environments, which has two critical implications:
- Fluid flows are laminar, not turbulent
- Transport is limited to diffusion and advection (travel along streamlines)
There is no shortage of methods for microfluidic mixing, but they all rely on the same phenomenon: changing the boundary conditions of the chamber. These boundary variations can be passive or active.
In passive mixing, the structure of the microchannel is tuned to increase contact area and contact time between various blocks of fluid, creating increased opportunity for
diffusion to occur. Passive mixing methods inclde microstructures, such as zigzag, serpentine/3D-serpentine or herringbone microchannels. Passive mixers have the advantage of not using any source of energy other than the bulk motion of the fluid. However, the quality of mixing decreases as the path length gets shorter, the flow rate decreases, and the feature sizes get coarser. Therefore, passive mixing strategies work best when sample volumes are large, and when high-precision fabrication techniques are available.
Active mixing mechanisms in microfluidic systems use an external force to drive fluid flow within a microfluidic system. Methods include microstirrers, flow pulsation, acoustic methods, and thermal and electrokinetic strategies. These methods can mix faster than passive methods, and mixing can be performed in very small volumes of static fluid. (One finding that’s relevant to our method, which uses active microposts: according to computational work, multiple small stirbars are better than one big stirbar.) However, active mixing requires that the mixer be driven externally, and the nature of the external force can present compatibility issues when combined with biological systems.
Optimizing microfluidic mixing for high-volume consumables
When designing high-volume consumables (e.g., diagnostic cartridges), it is typically desirable to minimize:
- Sample volume
- Complexity and precision of fluid handling
- Cost of goods, including tooling, assembly, and quality burden
Unfortunately, few microfluidic mixing methods help achieve these goals. Passive mixers require continuous flow, which drives up sample volume, and precise fluid paths, which drives up manufacturing costs. Active mixers vary widely in the design constraints they impose, but each has its own drawbacks. Microstirrers struggle without circular chambers and sample volumes smaller than ~100 µL, and because they must be individually loaded, they drive up assembly costs in multi-well cartridges. Thermal methods can induce local heating that can damage biological samples or change reaction kinetics. Acoustic methods use high-power ultrasound that can damage samples with shear stresses. They often involve trapping bubbles that must later be eliminated. Flow pulsation requires highly precise fluid handling. Electrokinetic mixing methods require integration of precise electrodes in the cartridge, driving up manufacturing costs.
Of course, here at Redbud Labs, we’re quite fond of MXR, the world’s first microfluidic mixing module designed specifically for integration into diagnostic consumables. It’s an active mixing method that we’ve packaged into a pop-in chip. Sample volumes are typically 10-100 µL (bigger and smaller are both fine), and it requires no external pumping or mixing. One chip can house multiple custom-sized chambers, which reduces the number of components and the cost of your bill of materials. To our knowledge, it’s the fastest mixing chip on the market, and the modular design makes it highly adaptable.
Making the call
When evaluating a microfluidic mixing method, here are some variables to consider regarding the underlying assay:
- How important is mixing to the quality of your assay, for example, due to reaction completeness or consistency?
- How important is mixing to the speed of your assay, for example, due to reagent or analyte dispersal?
- How long do you require mixing? Is power consumption or sample heating a potential issue in your assay?
- If you could remove all engineering constraints, what is the smallest sample volume permitted by the underlying biology or chemistry of your assay? What is the minimum sample permitted by your analytic method?
Here are some variables to consider regarding the design of the cartridge:
- What manufacturing methods do you hope to use for your cartridge? What are the minimum feature sizes?
- If you require mixing in multiple locations, how does the cost of your method scale with the addition of a new chamber?
- What is the anticipated yield and what are the assembly costs associated with your mixing method?
- What dead volume (if any) is required to service your mixing method?
- What (if any) fluid handling equipment is required to achieve the desired mixing performance?
Redbud Labs is here to help
If you’re designing a consumable cartridge and you’re looking for a microfluidic solution, we can help. We’re admittedly partial to our own microfluidic mixing chip, but we’re familiar with the full range of methods and we can help point you to the best solution. Looking to learn more? Contact us.