The microfluidics-based devices have intellectual roots in at least two diverse fields: microelectronics and bioanalytical chemistry. The computer chip paradigm inspired chemists and engineers to apply some of these same technologies to generate networks of channels through which fluids can be moved.
Not coincidentally, commercial microfluidics has its origins in California's Silicon Valley. The advent of microprocessors in the early 1970s and the subsequent development of highly integrated microelectronic devices later in the decade paved the way for microfluidics.
The application of microfluidics to the bioanalytical realm derives from work done in the late 1980's by Andreas Manz, then an analytical chemist at Ciba Geigy (now Novartis), who originated the TAS , an early lab-on-a-chip.
Manz envisioned the application of photolithography and chemical etching techniques for micromachining a complete microanalytical system on a chip to integrate sample preparation, chemical derivatization, electrophoretic separation, and detection using only nanoliters or picoliters of the test analyte.
In the course of investigating the TAS concept, Manz and his co-workers discovered that the phenomenon of electro-osmosis could be used to control the injection, flow and mixing of solutions.
Manz and coworkers joined forces with Jed Harrison's group (University of Alberta, Canada) to demonstrate the practicality of such a device. Their studies showed that channels 10m deep by 30m wide etched in glass could be used for capillary electrophoresis, offering high-resolution separations in as little as 15 seconds.
More importantly, they showed that creating electric potential differences across chip elements permitted the manipulation of flow and mixing of fluids. The combination of exceptionally fast separation times and miniscule sample sizes demonstrated that such micro-systems were not simply elegant curiosities, but had practical advantages as well.
The integration of nucleic acid sample preparation, amplification, and hybridization, became another technological goal for the microfluidics community during the 1990s.
The first major commercial thrust toward micro-scale nucleic acid target amplification originated from work done by Allen Northrup and co-workers (Lawrence Livermore Laboratory).2 They demonstrated that PCR reactions could run up to ten times faster in their micro-scale device than by conventional means.
Kricka and Wilding (University of Pennsylvania School of Medicine) independently devised a thermocycler capable of amplifying DNA contained in less than five microliters of solution.
In 1994, J. Michael Ramsey and co-workers (U.S. Department of Energy's Oak Ridge National Laboratory) began publishing a series of papers that extended the findings of Manz and Harrison and provided the fledgling microfluidics enterprise with some of its key intellectual property. The Ramsey group described a prototypical microfluidic device consisting of two perpendicular etched channels in the form of a cross with four reservoirs, one at each channel terminus.