Chemical and biological detection, analysis, and synthesis capabilities are of increasing importance for applications that include environmental analysis and remediation, process monitoring, emissions monitoring and control, medical tests, forensics and detection of chemical and biological weapons. Many of these applications are best done on site in the field, so portability and cost are nearly as important as is the performance of the setup. Unfortunately, most laboratory setups are, well, the size of a laboratory, and require expert operators. As such, they do not lend themselves to either routine or field applications. In order to provide these valuable functions to society, miniaturization and simplified operation of the chemical laboratory are badly needed.
Enter the lab-on-a-chip. A lab-on-a-chip is a MEMS (Micro Electro Mechanical System) device that combines microfluidic devices such as valves, pumps, pipes, and reaction vessels with control and sensor microelectronics to carry out a set of chemical reactions and/or analysis on a single chip. A lab-on-a-chip can be designed to gather and concentrate samples, analyze those samples with chemical sensors, high performance liquid chromatography, electrophoresis, mass spectrometry, flame ionization detectors, surface acoustic wave mass detectors with chemical selectivity, and many more.
MEMS technology for the lab-on-a-chip was developed to integrate microelectronics with mechanical devices, chemical sensors, pipes, pumps, valves, and reaction vessels on a common silicon substrate through microfabrication technology. While the electronics are fabricated in the same way as are conventional integrated circuits, the mechanical and chemical components are formed using lithographic micromachining processes that selectively etch the silicon wafer or add new structural layers to form the finished device. Economies of scale drive the cost of a production lab-on-a-chip to be orders of magnitude smaller than that to acquire the equivalent lab equipment.
The first application of MEMS technology to chemical analysis seems to have been the implementation of a gas chromatograph on a glass slide in 1979. Lack of supporting microfluidic devices prevented widespread application of this new technology until a complete infrastructure had been developed.
One of the first examples of a complete lab-on-a-chip, that is, a chip which could carry out a complex chemical analysis process, was the MicroChemLab developed around 2000 by researchers at Sandia National Laboratories in Albuquerque, NM.
Sandia’s MicroChemLab fits onto a silicon chip measuring about 4.5 cm by 1.5 cm. It integrates three microfabricated analysis stages. The first stage collects and concentrates the sample using a preconcentrator containing a micro hot plate to collect and concentrate chemical sensors. The micro hot plate is a resistive metal film grown on a silicon nitride membrane. A chemically selective coating is applied to the micro hot plate surface so that only the chemical species of interest are collected.
The second stage is a microscale gas chromatograph. The samples collected in the preconcentrator are released by rapid thermal desorption driven by applying a current pulse to the micro hot plate. The sample is then injected into the gas chromatograph. The gas chromatograph channel is made by etching a channel into the silicon surface which is typically 400 microns deep and 100 microns wide. The channel can be coated with chemically selective coatings to optimize the separation of the chemicals of interest. This column is formed in a spiral shape, which allows a 1 meter long channel to be fit on an area about the size of a nickel.
The final stage is an array of four chemical detectors. These consist of resonant crystals whose frequency changes as the sample adsorbs onto the crystal surface. Again, the crystal surfaces are coated so that each of the detectors is sensitive to different chemical groups.
Initially the MicroChemLab was used to separate and detect organic gases and volatile chemicals, but its usefulness has since been expanded to include pharmaceuticals, petrochemicals, and toxic industrial chemicals in concentrations as small as a part per million. Not only are the analyses carried out on a business card rather than in a room full of equipment, but the analysis is much faster than can be accomplished using laboratory-scale equipment.
Further development of the lab-on-a-chip has produced selective detection and analysis of airborne and waterborne germs and viruses and single cancer cells. The capability of cheaply carrying out many reactions or analyses in parallel, rather like using a multicore CPU, has led to new tools for genetic research, as well as chips which can synthesize and test large numbers of new drug candidates.
It seems likely that medical uses of lab-on-a-chip technology may soon become a practical addition to the armament of physicians. The earliest applications are likely to be the development of sophisticated diagnostic tools which would allow tests which currently require days in a medical laboratory to be accomplished in minutes in your doctor’s office. As the advent of treatments which are specially fitted to your personal genome continues, the lab-on-a-chip will offer rapid genetic analysis to guide the treatment plan.
Lower cost, point of use distribution, higher sensitivity, faster answers – the lab-on-a-chip offers dramatic changes for analytical chemistry, development of pharmaceuticals, and medical diagnosis and treatment. We should soon be reaping the first fruits of this new technology.
