The cover of Science, the 18 October 2002 edition, showing a prototype Integrated Fluidic Circuit with thousands of integrated valves.
If the term integrated fluidic circuit makes you think of a miniature device, packed with micro-mechanical parts for controlling tiny amounts of fluid, you've got the right idea. But making that image a practical reality required a paradigm shift.
In the 1970s engineers recognized that the principles that spawned the semiconductor industry could be applied to liquids and gasses. That is, integrated circuits and pathways could be used on a device to incorporate and miniaturize complex fluid-handling steps without loss of reliability.
Until recently, though, the reality of fluidic circuits has been thwarted because the material (silicon) and techniques used for making electronic circuits just don't work very well for making mechanical parts to control fluids. Imagine trying to stop water from draining from your kitchen sink with a dinner plate. The plate is too rigid to create a tight seal, much as silicon lacks the required deflective properties necessary to make microfluidic circuits. Some developers tried to use silicon for making microfluidic devices based on electro-osmotic flow, but this method turned out to be ineffective at regulating the mixing of fluids, without complicated workarounds.
In 1998, Dr. Stephen Quake and his group at the California Institute of Technology solved this problem through the development of a fabrication process called multilayer soft lithography. The process uses a rubber-like material, that deflects under pressure to create an effective seal. More importantly, the structures are so small that tens of thousands of them can be integrated into a dense network of channels for regulating aqueous solutions on a nanoliter and picoliter scale. The elegantly simple valve was later trademarked as the NanoFlex™ valve.
Integrated circuits (ICs) emerged in the 1970s as miniaturized devices that replaced bulky vacuum tubes in electrical equipment. Because we were struck by the similarities between ICs and our innovation, we modified the term integrated circuit as a term for our device—the integrated fluidic circuit (IFC).
While transistors control the amount and direction of current or voltage flowing into an IC, NanoFlex™ valves regulate liquid flows in an IFC.
An IC is designed to perform a particular electronic function. Much the same, an IFC is designed to combine substances that initiate a particular biochemical reaction. An IFC for a simple one-step assay requires only a simple network of valves and channels. A multi-step assay may require more sophisticated network patterns to flow one substance and then another.
In the 1970s, the first ICs contained transistors numbering in the tens. By the 1990s ICs had attained an exponentially higher level of performance—more than one million transistors on a single device. R&D milestones have demonstrated that valve density on an IFC has grown at a rate comparable to Moore's Law.
Both ICs and IFCs are devices whose components are fabricated in situ—that is, formed by layers of finely patterned material rather than assembled from many pieces. Therefore, they solve, for their respective applications, the problems that engineers deplore as the tyranny of numbers.
Just as integrated circuits (ICs) drove development of the computing industry, IFCs are uniquely positioned to drive development of large scale science through miniaturization and integration of biochemical operations on a small device. Thus, IFCs radically reduce reliance on bulky liquid-handling robots and microplates to accomplish the pipetting, incubation, detection, and analyses.