Microfluidics Evolution

When Caliper Technologies developed its microfluidic-based lab-on-a-chip (LOC) Bioanalyzer in the late-1990s, there was futuristic talk about how this device could be put into the home and people could use it to analyze a small blood sample every morning to see what foods/supplements they could take that day to optimize their physical well-being. Of course that application never made it to the marketplace, but Agilent Technologies, Santa Clara, Calif., bought the technology and continues to market its 2100 Bioanalyzer for sizing, quantification and quality control of DNA, RNA, proteins and cells. Results from the 2100 are delivered in less than 30 min in automated, high-quality digital formats.

The overall market for the entire biochip industry (which includes microarrays) is strong, with BCC Market Research estimating its total market in 2008 as $2.4 billion, which increased to $2.6 billion in 2009. BCC expects the market to grow at a compound annual growth rate (CAGR) of 17.7%, reaching $5.9 billion in 2014. For microfluidic LOCs specifically (a subset of the biochip market), the market for 2008 was $755 million, which then increased to $817 million in 2009. The LOC market is expected to have a five-year CAGR of 20.9%, reaching $2.1 billion in 2014. This forecast is in line with estimates by Yole Development, a European microsystem market research firm.

LOC devices have matured a lot since those first Caliper instruments introduced the basic technology to the marketplace. Agilent markets the 2100 as "one platform—endless possibilities." LOC devices bring the benefits of miniaturized, integrated and automated testing and analysis to numerous research-based industries, including genomics, biologicals (vaccines, blood, allergenics, gene therapy, tissues and various proteins isolated from humans, animals or microorganisms), histochemistry, fluorescence microscopy, drug discovery and preclinical development, environmental and forensics.

There are four basic steps in the 2100 Bioanalyzer’s operation: 1) the sample moves through the microchannels from the sample well (see picture below), 2) the sample is injected into the separation channel, 3) sample components are electrophoretically separated and 4) components are detected by their fluorescence and translated into gel-like images (bands) and electropherograms (peaks).
Because of their numerous applications, LOCs have attracted a multitude of suppliers and manufacturers offering all kinds of capabilities. From the full-scale LOC devices that can be integrated into standalone instruments like those from Agilent Technologies (shown below) to individual breadboard-type components to customized service houses, there are numerous suppliers to choose from. Then, there’s always the do-it-yourself researchers like the innovative students at the Stanford Microfluidics Laboratory (SML) at Stanford Univ., Palo Alto, Calif.

One of several research projects at SML involves the development of novel assays and portable instrumentation for label-free toxin detection. While GCMS and LCMS instruments are normally used for environmental monitoring, their size, sample prep and power requirements mostly limit their use to laboratory settings. To create a portable device to test for toxins in the field, Stanford’s Moran Bercovici and associates, in collaboration with the Univ. of Alberta’s Christopher Backhouse, developed an inexpensive handheld device (240 g) that utilizes microchip-based electrophoresis and isotachophoresis (ITP) with laser-induced fluorescence (LIF) detection. The resulting self-contained device integrates the functionality required for high voltage generation onto a microelectronic chip, includes LIF detection and is powered by a USB link connected to a laptop computer. The device has a limit of detection of 100 pM. "We also integrated several ITP assays in the device for label-free detection of a wide variety of chemicals, including chemical warfare agents, explosives and endocrine disruptors, with no requirement for sample processing," says Bercovici.