Manipulation of biological and/or chemical molecules in solution has become an essential aspect of various kinds of analysis. For instance, in biomedical or pharmaceutical assays, cellular components, proteins or nucleic acid (DNA) molecules are studied to ascertain particular genetic risk factors for disease or the efficacy of drug trials. Recently, a class of sample-receiving substrates has been developed for “microfluidic” bioassay devices, popularly called “lab-on-a-chip” devices. Lab-on-a-chip technology is exciting the interest of scientists in many areas. This technology can be used to carry out biological and clinical analyses, to perform combinatorial chemistry, and to carry out full-scale analyses from sample introduction to chemical separation and detection, on a single, miniaturized device efficiently and economically. Hence, microfluidic devices have recently gained great appeal in the biomedical, genomic, and pharmaceutical industries, where they offer the benefits for miniaturization, integration and automation. Substrates of these devices are integrated microfluidic assay systems with networks of chambers connected by channels, which have microscale dimensions, typically on the order of between 0.1 μm and 500 μm. These channels allow the movement of small volumes of reagent to assay stations. Such microfluidic substrates may be fabricated using photolithographic techniques similar to those used in the semi-conductor industry, and the resulting devices can be used to perform a variety of sophisticated chemical and biological analytical techniques.
Because of the variety of analytical techniques and potentially complex sample flow patterns that may be incorporated into particular microfluidic test substrates, significant demands may be placed on the analytical units, which support the test substrates. The analytical units not only have to manage the direction and timing of flow through the network of channels and reservoirs on the substrate, they may also have to provide one or more physical interactions with the samples at locations distributed around the substrate, including heating, cooling, exposure to light or other radiation, detection of light or other radiation or other emissions, measuring electrical/electrochemical signals, pH, and the like. The flow control management may also comprise a variety of interactions, including the patterned application of voltage, current, or power to the substrate (for electrokinetic flow control), or the application of pressure, vacuum, acoustic energy or other mechanical interventions for otherwise inducing flow.
As a consequence, a virtually infinite number of specific test formats may be incorporated into microfluidic test substrates. Because of such variety and complexity, many if not most of the test substrates will require specifically configured analyzers in order to perform a particular test. It is indeed possible that particular test substrates use more than one analyzer for performing different tests. The need to provide one dedicated analyzer for every substrate and test, however, will significantly reduce the flexibility and cost advantages of the microfluidic systems. Additionally, for a specifically configured analyzer, test substrates are generally only useful for performing a limited number of assay formats and functions. As the complexity and costs of test substrates increase, it becomes more desirable to increase the number of useful assay formats and functions for a particular test substrate-analyzer combination, or for a particular class of substrates in combination with a specifically configured analyzer.
For all their virtues, most current lab-on-a-chip devices, however, are inherently low throughput, allowing for only a small number of samples to be assayed at a time. Current microfluidic devices are limited typically to less than 40 or 50 assays per chip. Further, they are rather cumbersome to handle since they do not conform to standard robotics and often require manual processing. Therefore, it would be desirable to provide a high throughput microfluidic device that is configured to work with equipment for bio-chemical-genomic assays of an industry-standard format. Thus, as an aspect of the present invention, the device provides high-throughput microfluidic processing that is compatible with standard microtiter plate formats.