Microfluidic devices and systems have been developed that give researchers substantial advantages in terms of the miniaturization, automation and integration of a large number of different types of analytical operations. For example, continuous flow microfluidic devices have been developed that perform serial assays on extremely large numbers of different chemical compounds, e.g., for use in high-throughput pharmaceutical screening operations (see, e.g., U.S. Pat. Nos. 5,942,443 and 6,046,056). Other microfluidic devices have been developed that perform rapid molecular separations on a number of different samples in relatively short time frames (see, U.S. Pat. No. 5,976,336). All of these devices and systems share the ability to rapidly perform a wide range of different analytical operations.
Planar microfluidic analytical systems have a large number of advantages in terms of speed, accuracy and automatability. Despite these advantages, these planar channel systems suffer from a problem that is common to conventional capillary analytical systems. In particular, capillary systems, because of their extremely small volumes, can suffer from severely restricted sensitivity due to the simple lack of detectable amounts of material. For example, detection of materials in capillary or planar channel systems is typically accomplished by detecting signals from the channels in a direction orthogonal to the plane of the capillary or channel. This results in only the small amount of material that is present at the detection spot being subjected to the detection operation at any given time. In many cases, this deficiency is overcome using labeling techniques that have higher quantum yields of detectability, e.g., through fluorescence, chemiluminescence, radioactivity, etc. Of course, the use of these detection schemes requires the presence of a natural or added label that is detectable by these schemes. In many interesting analytical reactions, such labels are not readily available, or will themselves have a deleterious effect on the reaction to be analyzed.
As a result of reduced sensitivity, it previously has been difficult to utilize a number of different detection strategies in microfluidic systems, e.g., those strategies that have lower quantum detection yields or rely for sensitivity on the detection path length. For example, detection of low concentrations of analytes has been difficult in such systems, as has detection based upon non-fluorescent optical means, e.g., detection based upon absorbance.
Accordingly, it would be highly desirable to provide microfluidic systems that overcome these previously encountered shortcomings of microfluidic technology, namely, systems that have enhanced sensitivity for optical detection. The present invention meets these and a variety of other needs.