Microfluidics is an area of microfabrication that focuses on the manipulation of liquids and gases in channels with cross-sectional dimensions ranging from a few nanometers to hundreds of micrometers. Microfluidics is a rapidly growing technology impacting a number of research areas including chemical sciences, biomedical research, and drug discovery. Applications include but are not limited to genomics, proteomics, pharmaceutical research, processing of nucleic acids, forensic analysis, cellular analysis, and environmental monitoring, among others.
One of the primary focuses of microfluidic technology is directed toward making increasingly complex systems of channels with greater sophistication and fluid-handling capabilities.
Some of the first microfluidic devices were fabricated using conventional techniques that originated from the microelectronics and integrated circuit industry. Such devices were typically made in glass, silicon or quartz.
Processes that were originally designed for microelectronics, such as standard photolithographic methods, were then applied to glass or silicon substrates in order to build two-dimensional channel networks for sample transport, separation, mixing and detection systems on a monolithic chip.
To illustrate an example of an earlier process for microfluidic device fabrication based on silicon and glass substrates, a mask is prepared having both transparent and opaque regions that are patterned as a negative image of the desired channel design. A UV-light source transfers a design from the mask to a photoresist (analogous to photographic film) that was previously deposited on the substrate using traditional spin-coating methods. The photoresist is then developed in a solvent that selectively removes either the exposed or the unexposed regions. The open areas are then chemically etched into the substrate, whereby the etching time, etching conditions and crystalline orientation of the substrate control the depth of the channels and the shape of the sidewalls, respectively. Finally, the photoresist is removed and the channel system is closed by thermally bonding the patterned substrate to a cover plate.
More complex, three-dimensional systems can then be built by bonding several of these patterned layers together.
Although the above described microfluidic device fabrication and layering process based on glass and silicon substrates has some benefits, it also embodies several limitations that include, but are not limited to: (1) material limitations related to the use of glass substrates; (2) material costs; (3) the many processing steps involved; (4) limitations in geometrical design due to the isotropicity of the etching process; and (5) surface chemistry limitations with respect to silicon substrates. Each of these is discussed below.
First, the bonding of glass plates together leads to an evident source of defects and low device yields. The ability to build onto structures that have large surface topographies is impractical due to the requirement that the layers be extremely flat.
A further limitation to the glass bonding technique is that the construction of metal lines and other structures into the glass layer is very difficult, which can lead to several problems with the integration of electrical and non-electrical components on more complex devices.
In addition, when considering developing a microfluidic device fabrication process for large-scale manufacturing, the cost of substrate material is a significant factor in any high volume production. The cost of an average silicon or glass substrate can be anywhere from double the cost to twenty times as much as the cost of, for example, alternate substrate materials such as polymers.
Furthermore, microfluidic device fabrication based on silicon and glass substrates involve many processing steps (e.g. cleaning, resist coating, photolithography, development, wet etching) as described in part in the paragraphs directly above. Even though these steps can be automated in some instances, each microfluidic device must complete this fabrication process serially, which as a result increases time, overall costs, as well as the risk of manufacturing and/or human error.
Microfluidic device fabrication based on silicon and glass substrates also have geometrical design constraints due to the isotropicity of the etching process. Depending on the etching mechanism used, the shape of the patterned channel is controlled by the chemistry of the etch, etching time, and the substrate used. For many applications, different channel cross sections (such as high aspect ratio square channels) may be desirable.
Finally, the surface chemistry of silicon substrates also poses a problem, especially for continuous flow systems. For example, biomolecules tend to create a bond to silicon surface groups and therefore stick to the silicon substrate surfaces. While this can be prevented by employing a surface coating, it carries with it the added time, expenses and risks that go with an additional process step.
Thus, there is a need addressed by embodiments of the present disclosure for a method of fabricating three dimensional microfluidic devices that overcomes these limitations and, in particular, eliminates the need of expensive microlithography equipment to perforin the processing, is relatively inexpensive, is capable of use for applications operating at temperatures above 65° C., and includes metal lines in its construction.
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