The area of miniaturized microfluidic technology, also known as “lab-on-a-chip” or “micro total analysis systems”, is rapidly expanding with the promise of revolutionizing chemical analysis and offering enabling tools and technologies for the life sciences. The majority of molecules and compounds of interest in the life sciences are in the liquid phase and typically analytical measurements are used to conduct quantitative and qualitative trace analysis of these analytes in solution. However, due to the nature and origin of the materials under analysis, sample amounts and volumes are historically in short supply and these amounts are constantly decreasing. Moreover, as seen in drug discovery and drug development, including pharmacokinetic and proteomics applications, the need for better analytical measurements that require smaller amounts and volumes of sample is growing. Inherently, microfluidics are a “good fit” for the move to both smaller sample and volume requirements. In fact, a primary reason for miniaturization has been to enhance analytical performance of the device rather than reduce its physical size. Additionally, the ability to miniaturize the analysis with the use of microfluidics allows for integration of multiple separation techniques that enable parallel processing and also for the incorporation of several types of analytical measurements in a single device (sample handling, injections, 2D separations, reaction chambers etc.). Inherently, there are other benefits that accompany miniaturization, such as reduction in reagent and waste disposal, as well as, the reduction of the device footprint.
The first analytical miniaturized device was a gas chromatograph fabricated in silicon over 25 years ago. This device was designed for separating components in the gas phase. A decade later, components of a liquid chromatography column were fabricated on a silicon chip. Most early work related to miniaturization on silicon and the research focused on the fabrication of components such as microvalves, micropumps, and chemical sensors. None of the early systems implemented integrated electronics or electric fields for operation, but rather the silicon was used as a substrate for micromachining desired shapes/geometry.
Most methods used in microfabrication were developed in the 1970's and 1980's in the silicon microprocessor industry. Typically, initial research developments were fabricated in silicon because of the extensive knowledge and tools available for silicon processing. This approach works satisfactorily for devices used for “dry” analyses, however, many microfluidic devices require the integration of on-chip electronics and/or the ability to apply electric fields to device. Because most applications in the life sciences involve samples contained in the liquid phase, the majority of micro analysis systems being developed/designed are for analysis of analytes contained in solution. The need for the ability to apply electric fields to the device becomes a serious issue when processing samples contained in the liquid phase on silicon substrates.
A difficult scenario is encountered due to the opposing objectives of the micro total analysis system and the microprocessor technology used to make them. Typically, the microprocessor industry strives to keep microdevices “dry” and “clean” as liquids, moisture, and contaminates interfere with the device performance and operation. This highly contrasts the needs of micro total analysis systems where liquids and foreign substances (analytes, including salts) are deliberately introduced to the device. Again, this does not pose a problem for a silicon device that does not involve electronic or electrical field generation where only specific geometries are micromachined. However, major issues arise when electronics are incorporated in the devices and especially when potentials are applied for the generation of electric fields (semiconductor must be insulated for controlled electric field generation).
There is currently a move to perform chemical separations on-chip with the use of electric fields, for example applications such as CE, CEC, charged analyte manipulation, and charged solution manipulation. Because of the relatively strong fields needed for the separation process, research has moved to considering non-conductive substrates such as glass, quartz, and non-conducting polymers as opposed to the use of silicon as in the manufacture of semiconductors. This shift in materials is warranted because in order to form the electric fields, the substrates must be insulated in the desired areas.
Although there are conventional techniques for insulating silicon substrates, the dielectric coatings currently available are designed for the electronics industry and operate under “dry” conditions. Much effort in the microprocessor industry has been expended on keeping devices dry or isolated from liquids. Additionally, the microprocessor industry has gone to great lengths to avoid contact of the electronic device with mobile ions such as salts due to the destructive nature they pose to dielectric coatings used to insulate the silicon used in microprocessors.
Microfluidic devices requiring the application of relatively high voltages and electric fields for the manipulation of liquids and samples are mainly fabricated on insulating substrates because of their insulating properties. Application of high voltages to liquids on insulators on conductor substrates often leads to shorting or drastically reduced performance and lifetime of desired electrical properties.
Accordingly, the art needs dielectric coatings that do not degrade, but rather maintain their electrical properties when exposed to direct voltage application and high electric field strengths while in the presence of high humidity and/or direct liquid contact (wet). The art needs to overcome current coating technology limitations and provide appropriate solutions for microfluidic device applications. The art needs microfluidic devices that take advantage of the highly developed silicon processing techniques for silicon and other substrates including micromachining as well as electronic circuit integration and electric field definition. The art lacks the ability to incorporate microfluidics and electronics in the same substrate allowing for fully integrated systems.