Cell encapsulation with Dolomite microfluidic device. (Image Credit: Dolomite Microfluidics)
Interest in microfluidics technology began as far back at 1975, when researchers at Stanford Univ. developed a miniature gas chromatograph fabricated on a silicon wafer. The technology advanced rapidly during the 1990s, when the first commercial lab-on-a-chip system was launched.
Since microfluidics origin, chemists and engineers have used microelectronics and analytical biochemistry concepts to generate microfluidic chips with networks of channels through which fluids move, allowing a range of analytical, synthetic and other fluidic tasks to be performed. In microfluidics, there are two main branches: lab-on-a-chip and benchtop analytical instrumentation. Lab-on-a- chip devices are small, low-power devices that integrate functions like dispensing, mixing, separation and detection, and are used in medical diagnostics and other applications. Benchtop analytical instruments are larger, high-power devices that use microfluidic technology to boost the speed of analysis.
Microfluidics in the life science industry
The pharmaceutical industry uses microfluidics to overcome issues with poor aqueous encapsulation rates and size heterogeneity during bioencapsulation. “Thousands of droplets can be generated per second with high particle size homogeneity and increased encapsulation efficiency, and single cells can be encapsulated,” says Mike Hawes, Chief Commercial Officer, Dolomite Microfluidics. Typically applications are cell sorting, protein analysis, high-throughput assays and next-generation sequencing.
In health care, microfluidics is influencing developments in molecular biology, drug delivery and discovery, diagnostics, forensics, analytical methods and nucleic acid analysis. PCR reactions can be performed up to 10 times faster with current microfluidic technology, and thermocyclers can amplify DNA contained in less than 5 μL of solution, enabling parallel processing of multiple trace samples. Microfluidics is also used for drug development studies of multicellular organisms.
And, over the past few years, several companies have been working to commercialize microfluidic technologies for automated multiple sample analyses. Fluidigm has integrated pneumatic rubber valves in microfluidic circuits to commercialize digital PCR and single-cell manipulations. RainDance Technologies Inc. has developed a single-molecule picodroplet system for digital PCR. These picodroplets are compatible with PCR machines and next-generation sequencers. And, recently, Advanced Liquid Logic Inc., now Illumina, has developed electro-wetting technology that manipulates discrete droplets in a microfluidic device without pumps, valves or channels. Illumina has also released its Neoprep microfluidics system to automate sample preparation for its next-generation sequencing platform.
Microfluidics in the materials science industry
In particle manufacture, microfluidic methods are used to create nanostructured materials. This can lead to the development of “smart” materials, such as those for self-healing or sustained release, novel tissue scaffolds, composites and nanocomposites, ultrasound contrast agents and quantum dots.
“Another class of small-volume materials science is based on handling dangerous, toxic and explosive reagents,” says Hawes. “Supercritical microfluidics combines the advantage of size reduction with the unique properties of supercritical fluids, opening new chemical possibilities, supercritical water and carbon dioxide.” It also enables synthesis of high-quality nanocrystals; controlled, lowtemperature reactions between explosive reactants; and investigation of exothermic reactions and novel chemistry applications.
Microfluidics in materials science is also offering fabrication of polymeric particles that can be used in a variety of applications, such as systems for controlled chemical release, optical materials, media and various biological applications. “Microfluidic chips can provide physical and chemical properties of polymeric particles, such as their shape, size, porosity, surface charge and hydrophilicity or hydrophobicity, that influence the particle function,” says Krystyna Hohenauer, Portfolio Director, Automation and Microfluidics, PerkinElmer.
A game-changer for science
Microfluidic technology shrinks the scale down to nanoliter and picoliter volumes of biological samples. These devices can be fabricated from various types of glass, polymers and silicon, and can operate at picoliter sample sizes, yielding faster reactions and separations.
“Integration of automation with microfluidics allows multiple sample analyses with reduced manual labor and time,” says Hohenauer. “Hence, microfluidics offers new tools in material science genomics, proteomics, drug discovery, high-content imaging and next-generation sequencing applications.”
From a life science perspective, microfluidic technology offers rapid analysis times, integration of multiple processing steps and uses very small sample and volumes, decreasing costs and enabling small quantities of precious samples to be stretched further. “The quantities are also reduced,” says Hawes. “Low thermal mass and high surface-to-volume ratio facilitate rapid heat transfer, enabling quick temperature changes, precise temperature control and thermal gradients, all on a chip.”
Overall, microfluidic technology leads to developing specific features that make the product an interesting and competitive offering with improvements in the performance of end products, according to Hohenauer.
Academic researchers are now focusing on delivering fully integrated products with specific applications. Microfluidic methods are adapting toward the fact that their intended use must surpass the existing technology in performance and capability, or offer the results at a low cost. “New commercial and research landscapes require microfluidics to target niche markets, where existing technologies don’t address specific customer needs. They also reduce market entry barriers and facilitate the commercialization of microfluidic technologies,” says Hohenauer.
What’s still needed
Over 15 years, several academic and commercial entities have been working to develop microfluidics technologies that allow automation and multiplexing of laboratory equipment screening technologies and in vitro diagnostic devices. The applications require fundamental knowledge in molecular transport and reactions at microscale-length scales. “Based on this knowledge, many innovative microfluidic pathways to obtain desired molecular transport and reaction can then be developed,” says PerkinElmer’s Hohenauer.
Construction and design of microfluidic devices is complex and it’s not possible to simply scale down from macrodevices. “Successful implementation of microfluidic technology requires extensive basic research, tight quality control in manufacturing and the know-how no single organization possesses,” says Hawes. “Consequently, products from commercial organizations have been slow to have the broad and rapid impact that was expected in the euphoria of the late 1990s.”
Early microfluidic devices were usually made from glass, quartz or silicon, which are amenable to structuring via photolithography and wet-etching. “While these offer the best size tolerances, newer materials, such as polymers, have caught the attention for their potential low cost,” says Hawes. Technological gaps preventing commercial uptake and the lack of standardization need to be addressed. “Users must also understand science and technology are distinct and out of sync in any technology transfer from R&D to commercial product,” continues Hawes.
Microfluidics applications are limitless, and their future will focus on their integration into new commercial products, especially in the life science industry. However, most important is microfluidic technology’s potential in automated sample preparation, according to Hohenauer.
“Today, research and clinical laboratories spend hours of manual labor in sample collection, sample pre-treatment, sample concentration and buffer exchanges,” says Hohenauer. “Microfluidics innovations are needed to improve the quality and selection of biomolecules available in these samples.”
Microfluidics platforms will be able to generate clinical answers from single-cell genomics and proteomics analysis in the future. With the rise of data connectivity and personal wireless devices, the future of microfluidics must be integrated with software/hardware features offered by these devices.