Nanochemistry on a Plastic Slide:
NIST Research Supports Biochip Technology

There well may be a plastic biochip in your future, thanks in part to the National Institute of Standards and Technology. Microfluidic devices, also known as “lab-on-a-chip” systems, are miniaturized chemical and biochemical analyzers that one day may be used for quick, inexpensive tests in physicians’ offices. Most microfluidic devices today are made of glass materials. Cheaper, disposable devices could be made of plastics, but their properties are not yet well understood for these applications.

The primary advantage of such systems—other than cost—is the ability to analyze very small samples. With just a few picoliters (trillionths of a liter) of water, blood, DNA, spinal fluid, or other sample, these tiny devices can be used to sequence DNA, detect toxic chemicals, or identify harmful bacteria. Detection limits range from the part-per-million level down to, in some cases, single molecules. In the future, this may mean using just a single drop of blood rather than a whole test tube full to screen patients for biomarkers of disease or to test soldiers in the field for exposure to toxic chemicals. (In fact, a single drop of blood may provide hundreds of samples for these lab-on-a-chip devices.)

Plastic biochips are made of materials like acrylic, polystyrene, or co-polyester and are etched or indented with channels ranging in size from 20 micrometers to 50 micrometers wide in a variety of shapes—round, square, trapezoidal. Networks of channels can be used to flow the tiny fluid samples sequentially through a variety of processes, including mixing, heating, or chemical separations such as microchromatography or microelectrophoresis. A key need for accelerating commercialization of the technology is detailed understanding of the flow and mixing of fluids within the microchannels.

NIST is contributing on a number of fronts. One study looked at how fluids flowed in plastic microchannels by tracking fluorescent dye in the fluids. NIST researchers also developed an easy technique for accurately measuring fluid temperatures—an important parameter for chemical reactions. Biochips used for analyzing DNA, for example, must be able to repeatedly heat samples to specific temperatures to carry out a miniature version of PCR, a method for “copying” DNA segments.

A third project spawned a method for concentrating and separating molecules such as amino acids, proteins, or DNA within microchannels. The technique concentrates the molecules as much as 10,000-fold or more, making it easier to analyze extremely dilute samples (concentrations of picomoles per liter or less).

Finally, NIST staff designed a novel system to overcome the difficult problem of slow mixing in microfluidic devices. The mixer consists of a T-shaped microchannel imprinted in plastic that is modified with a laser to create a series of slanted wells. The wells speed the mixing of two streams entering the passage.

For further information contact: Laurie Locascio, laurie.locascio@nist.gov, David Ross, david.ross@nist.gov, or Michael Gaitan, michael.gaitan@nist.gov.

Selected Publications

Esch, M.B.; Locascio, L.E.; Tarlov, M.J.; Baumner, A.; Durst, R.A. “Detection of Viable Cryptosporidium parvum using DNA Probes and Liposomes in a Microfluidic Chip,” Analytical Chemistry 73(13), 2952-2958 (2001).

Wimmer, R.F.; Waddell, E.; Barker, S.L.R.B.; Suggs, A.; Locascio, L.; Love, B.J.; Love, N.G. “Development of an Upset Early Warning Device to Predict

Defloculation Events,” Proceedings of the Water Environment Federation Conference and Exposition (2001).

Ross, D.; Gaitan, M.; Locascio, L.E. “Temperature Measurement in Microfluidic Systems Using a Temperature-Dependent Fluorescent Dye,” Analytical Chemistry 73(17), 4117-4123 (2001).

Johnson, T.J.; Ross, D.; Locascio L.E. “Rapid Microfluidic Mixer,” Analytical Chemistry 74(1), 45-51 (2002).

Ross, D.; Locascio, L.E. “Microfluidic Temperature Gradient Focusing,” Analytical Chemistry 74(11), 2556-2564 (2002).

The stained bacterial cells shown above are adhering to posts constructed within microscopic channels of a plastic sensor device. The turquoise, green, yellow and orange colors reflect increasing densities of e. coli cells, which eject potassium in the presence of certain chemicals.

Using fluorescent dyes that get brighter as they heat up, NIST researchers developed a technique for accurately measuring the temperatures of microfluidic constriction points. The temperatures shown here
(top to bottom) are approximately 40 °C, 60 °C, and 80 °C, respectively.

Another technique using fluorescent dyes shows a sample moving through a microchannel. By selecting the right plastic materials, coatings, and flow conditions, researchers can minimize broadening or smearing of the sample as it moves through a microchannel, thereby improving the accuracy of analytical results.