This invention relates generally to miniaturized genetic, biochemical and chemical processes related to analysis, synthesis and purification procedures. Specifically, the invention provides an apparatus and method for moving liquid droplets across a surface through the use of electrostatic activation with no moving parts other than the liquid droplets themselves.
It must be appreciated that the present invention may have utility in any situation where controlled motion and/or deformation of liquid droplets is needed. One example is merging of two droplets into one. This example is especially advantageous for facilitating chemical reactions or mixtures between fluids of small volume. Examples of fluids are liquids, liquid solutions and emulsions, particulate solid-liquid emulsions and particulate solid-liquid suspensions. The small-volume fluid moving capability of the present invention enables small device size and therefore enables large-number arrays of drop movers for massively parallel handling of droplets, as required for combinatorial approaches to material discovery or synthesis. Combinatorial chemistry is suitable for material discovery or synthesis in a number of fields and industries, but especially in bioscience. It has become increasingly desirable in recent years to develop capabilities for rapidly and reliably carrying out chemical and biochemical reactions in large numbers using small quantities of samples and reagents. For example, pharmaceutical researchers as well as chemical, bioscience, and biomedical researchers have turned to massively parallel screening of combinatorial libraries as sources of new lead compounds for drug discovery. A combinatorial library is a collection of chemical compounds, which have been generated, by either chemical synthesis or biological synthesis, by combining a number of chemical “building blocks” as reagents. For example, a combinatorial polypeptide library is formed by combining a set of amino acids in every possible way for a given compound length (i.e., the number of amino acids in a polypeptide compound). Millions of chemical compounds can theoretically be synthesized through such combinatorial mixing of chemical building blocks.
Once a library has been constructed, it must be screened to identify compounds which possess some kind of biological or pharmacological activity. Through the years, the pharmaceutical industry has increasingly relied on high throughput screening (HTS) of libraries of chemical compounds to find drug candidates. HTS describes a method where many discrete compounds are tested in parallel so that large numbers of test compounds are screened for biological activity simultaneously or nearly simultaneously. Currently, the most widely established techniques utilize 96-well microtitre plates. In this format, 96 independent tests are performed simultaneously on a single 8 cm×12 cm plastic plate that contains 96 reaction wells. These wells typically require assay volumes that range from 50 to 500 μl. In addition to the plates, many instruments, materials, pipettors, robotics, plate washers and plate readers are commercially available to fit the 96-well format to a wide range of homogeneous and heterogeneous assays. Recently, the microtiter plate approach has been extended to 384 and 1536 well formats. However, there is a point at which the cost in miniaturization of plates and redesign of associated equipment has inherent costs and complexities that limit such an approach to miniaturization.
The following disclosures may be relevant and/or helpful in providing an understanding of some aspect of the present invention:
U.S. Pat. No. 6,040,193 to Winkler et al., (“Combinatorial Strategies for Polymer Synthesis”) teaches a series of channels, grooves, or spots are formed on or adjacent a substrate. Reagents are selectively flowed through or deposited in the channels, grooves, or spots, forming an array having different compounds at selected locations on the substrate.
U.S. Pat. No. 6,284,113 to Bjornson et al., (“Apparatus and Method for Transferring Liquids”) discloses a transfer plate having a plurality of apertures, which act as transfer elements. Each aperture is capable of being electrically activated. The transfer plate is attached to a multiwell plate to form a sealed system except for the apertures of the transfer elements. The transfer plate is adapted for simultaneously transferring precise amounts of a liquid from the multiwell plate to a sample receiving plate by electrically activating the apertures in the transfer plate.
U.S. Pat. No. 6,319,469 to Mian et al., (“Devices and Methods for Using Centripetal Acceleration to Drive Fluid Movement in a Microfluidics System”) teaches a system comprising a combination of two elements, a rotatable micro-platform and a micro-manipulation device. The micro-platform is preferably a disk that includes sample, inlet ports, fluid micro-channels, reagent reservoirs, reaction chambers, detection chambers, fluid inlet ports, air outlet ports, air displacement channels, and sample outlet ports. The disk is rotated at speeds from about 1–30,000 rpm to generate centripetal acceleration that enables fluid movement. The inlet ports allow samples to enter the disk for processing and/or analysis. The air outlet ports and the air displacement ports provide a means for fluids to displace air, thus ensuring uninhibited movement of fluids on the disk. Specific sites on the disk also preferably comprise elements that allow fluids to be analyzed, including thermal sources, light sources, and acoustic sources, as well as detectors for each of these effectors.