Advances in development of lab-on-chip devices, which shrink and potentially simplify laboratory tests like DNA analysis, have largely been tempered by the inherent complexity of the systems they are trying to replace. DNA analysis usually requires a laboratory full of instruments and several days to obtain results.
But now a team of researchers at Arizona State University report that they have made several advances in the area of microfluidic component design, fabrication and integration, bringing the technology to the point where DNA analysis could be done simply and in significantly less time than required today. The researchers are borrowing their ideas from what has become the king of small-scale integration – microelectronic integrated circuits (IC).
“We’ve basically taken some of the primary ideas of electronic integration and applied them to microfluidic devices. This new platform is called microfluidic IC,” said Robin Liu, project manager at the Center for Applied Nano-Bioscience (ANBC) at the Arizona Bio Design Institute. “The novelty here is instead of having electrons flow between electronic chips, with microfluidics we have very tiny amounts of fluid moving between chips.”
Liu and his colleagues detail their research findings in an article, “Development of integrated microfluidic system for genetic analysis.” The article is the cover story of the October 2003 SPIE Journal of Microlithography, Microfabrication and Microsystems.
Liu said the advantages of integrated microfluidic devices include being able to build sophisticated devices from relatively simple parts, modularity of components, standardization of microfluidic chips and the ability to plug in and unplug specific parts of an overall system.
“Traditionally, every time you change the bioassay procedure in a microfluidic device, you have to redesign a whole chip,” he explained. “This complicates everything, because then the fabrication process has to be changed, the integration has to be changed, the design has to be changed, everything has to be changed.
“Using an integrated circuit approach, we can exchange one of the components simply by unplugging it and plugging in a different one to achieve different functionalities of the overall system,” Liu said. “It is a very flexible platform and any time you need to change the assay (a specific test) or you need to change the reactions, you just unplug the module and plug in a different module.”
The article describes several approaches to the integration of complex functionalities in microfluidics. They include development of micromixers, microvalves, cell capture, micro polymerase chain reaction devices and new methods for making intricate, minute parts out of plastics.
But it is the integration, the bringing together of these disparate parts, to work in one overall, yet minute operating system, that is the most important advance, Liu said.
“From an integrations standpoint this simplifies assembly,” he said. “Instead of putting every component onto a single device, one chip can be a microvalve, one chip can be a micropump. We actually build the overall system by assembling the pieces.
“Hopefully, this will be the standard procedure for microfluidics in the future,” he added. “Just like the integrated circuit is the standard for microelectronics.”
The end result would be a microfluidic device that can dramatically simplify some laboratory analysis procedures. For example, such a microfluidic device could be used to provide direct sample-to-answer analysis of DNA samples. That is, a lab technician would put a patient’s blood in one end of the device and it would provide DNA data (in hours or minutes instead of days) showing if the patient has a certain disease, cancer or HIV.
Such a fully integrated device would require no external pressure sources, fluid storage, mechanical pumps, or valves that are necessary for fluid manipulation, eliminating possible sample contamination and simplifying device operation. This device provides a cost effective solution to direct sample-to-answer genetic analysis, and thus has potential impact in the fields of rapid disease diagnostics, environmental testing and biological warfare detection.
ANBC, led by Frederic Zenhausern, applies advances in microfluidic technology to integrate all the necessary steps of nucleic acid analysis to enable molecular diagnostic systems. For example, ANBC is partnering with the Mayo Clinic, and IBM Life Sciences and the Translational Genomics Research Institute, to develop an integrated “nano-genomic” device for melanoma studies.