Bio-MEMS - History

History

In 1967, S. B. Carter reported the use of shadow-evaporated palladium islands for cell attachment. After this first bio-MEMS study, subsequent development in the field was slow for around 20 years. In 1985, Unipath Inc. commercialized ClearBlue, a pregnancy test still used today and can be considered the first microfluidic device containing paper and the first microfluidic product to market. In 1990, Andreas Manz and H. Michael Widmer from Ciba-Geigy (now Novartis), Switzerland first coined the term micro total analysis system (μTAS) in their seminal paper proposing the use of miniaturized total chemical analysis systems for chemical sensing. There have been three major motivating factors behind the concept of μTAS. Firstly, drug discovery in the last decades leading up to the 1990s had been limited due to the time and cost of running many chromatographic analyses in parallel on macroscopic equipment. Secondly, the Human Genome Project (HGP), which started in October 1990, created demand for improvements in DNA sequencing capacity. Capillary electrophoresis thus became a focus for chemical and DNA separation. Thirdly, DARPA of the US Department of Defense supported a series of microfluidic research programs in the 1990s after realizing there was a need to develop field-deployable microsystems for the detection of chemical and biological agents that were potential military and terrorist threats. Researchers started to use photolithography equipment for microfabrication of microeletromechanical systems (MEMS) as inherited from the microelectronics industry. At the time, the application of MEMS to biology was limited because this technology was optimized for silicon or glass wafers and used solvent-based photoresists that were not compatible with biological material. In 1993, George M. Whitesides, a Harvard chemist, introduced inexpensive PDMS-based microfabrication and this revolutionized the bio-MEMS field. Since then, the field of bio-MEMS has exploded. Selected major technical achievements during bio-MEMS development of the 1990s include:

• In 1991, the first oligonucleotide chip was developed
• In 1998, the first solid microneedles were developed for drug delivery
• In 1998, the first continuous-flow polymerase chain reaction chip was developed
• In 1999, the first demonstration of heterogeneous laminar flows for selective treatment of cells in microchannels

Today, hydrogels such as agarose, biocompatible photoresists, and self-assembly are key areas of research in improving bio-MEMS as replacements or complements to PDMS.