Biologists and clinical biochemists routinely use microfluidic systems to scale down a number of laboratory techniques. These devices have one or more channels with at least one dimension of less than 1 mm. Common fluids used in microfluidic devices include whole blood samples, bacterial cell suspensions, and protein and antibody solutions.
Microfluidic devices can be used to make a variety of measurements, including molecular diffusion coefficients, fluid viscosity, chemical binding coefficients and enzyme reaction kinetics. Other applications include capillary electrophoresis, immunoassays, mass spectrometry of proteins, DNA analysis and cell manipulation.
Although applications for microfluidic systems are numerous, the design of the devices has remained relatively unchanged since they were first invented over a decade ago. Now, however, Emil Kartalov and colleagues report on a fundamental technological advance that allows microfluidic devices to become more structurally complex, which opens the way for even more applications. The USC/Caltech scientists have called their new system a "via" because of its similarity to modern semiconductor electronics.
Fluid highways
The vias are vertical micropassages that connect channels fabricated in different layers on the same multilayer chip. This allows channels to cross without mixing, thus drastically expanding the number of possible fluidic architectures while at the same time making devices smaller and denser. "Our vias do for microfluidics what overpasses and underpasses do for a highway," Kartalov told medicalphysicsweb. "Imagine what traffic would look like if roads could not use such structures and had to have traffic lights at every resulting intersection."
The new 3D structures could also be important for printing nested bioarrays in inexpensive and easy ways. Moreover, the ability of a channel to "leave" its layer means that the same channel can act as a reagent channel in one part of the chip and as a control channel in another part. "This feature means the channel could be used to make new 'autoregulatory' devices," said Kartalov. "Such systems might even form the basis of analogue fluidic logic and computing circuitry."
The researchers made their multilayer microfluidic devices by pouring or spinning uncured PDMS (polydimethylsiloxane) on silicon wafer moulds, where the features are defined by photolithography. After partial curing, the PDMS layer is peeled off the mould and stacked onto another PDMS layer - "like pancakes on a platter", says Kartalov. Grooves left by the photoresists in the upper PDMS layer now become microfluidic channels and they are closed off at the bottom by the lower PDMS layer. Further curing binds the layers together and allows the channels to hold together under pressure.
Previously, multilayer devices were produced so that each channel always remained in its own layer. "What we report is a new way to connect these channels vertically," said Kartalov. "The trick is to use a mould with features of different height, and spin the PDMS at thicknesses smaller than the height of the taller features but larger than the height of the lower feature."
It turns out that just three layers are enough to print a "superarray" of nested bioarrays, a technique that is similar to how microprocessors are fabricated. "The idea is to print multiple copies (or nested arrays) of the same antibody tests, for example, then peel off the chip, dice the substrate, and have a large number of inexpensively printed identical test matrices, each one of which can be used for a different sample," explained Kartalov. "Each such nested array can then be inserted as the centrepiece of a chip onto a particular diagnostic panel. This parallel printing could also be faster and cheaper than conventional means."
Briefing: microfluidics for the developing world
Microfluidics will form the basis of cheap, easy-to-use diagnostic systems suitable for use in the developing world, according to a recent review in Nature (442 412). A team of scientists from the University of Washington (Seattle, WA) is working to develop microfluidic devices that can easily identify a variety of diseases without the need for air-conditioned laboratories, refrigerators, electricity or highly trained personnel. They claim that such devices will revolutionize health care in regions such as rural Africa.
Microfluidics deals with the behaviour and manipulation of microscale or nanoscale volumes of fluids. At these scales, the physics of fluids can be very different from the macroscopic scales we are used to. Factors such as surface tension, energy dissipation and fluidic resistance start to dominate the system and cause some interesting and counterintuitive properties to appear. Turbulence, for example, is extremely low, so two fluids joining will not mix.
These principles can be exploited in the design of miniature lab-on-a-chip systems, which integrate several laboratory functions on a single chip. Such devices handle extremely small fluid volumes in order to perform chemical or biological analyses. "Microfluidic systems allow miniaturization and integration of complex functions, which could move sophisticated diagnostic tools out of the developed-world laboratory," explained Paul Yager and colleagues in their review article.
The authors continued: "Microfluidic diagnostic technology has the potential to perform assays at sensitivity, specificity and reproducibility levels similar to those of central laboratory analysers...Global health programmes are significantly hindered because such tests are currently unavailable."
The Bill and Melinda Gates Foundation is currently supporting the development of prototypes of a hand-held reader system intended to work with disposable microfluidic chips. This will enable the simultaneous diagnosis of diseases such as malaria, typhoid and dengue fever with only a couple of drops of blood from the patient. We can expect to see the introduction of such devices specifically designed for the developing world within the next five years, according to the review.