Fluid delivery and removal of micron scale structures is a commonly used technique which has many technical applications. For example, certain techniques for the analysis of biological molecules in a sample involve the fluid delivery of numerous micron scale beads or spheres having attached to their surfaces different chemical functional groups to a substrate having numerous discrete sites that can bind or hold the micron scale materials to form what is generally known as an array. Such fluid delivery is often inefficient since the fluid itself often removes a measurable portion of the micron scale structure from the discrete sites before they can be utilized for their intended use. Because of this, only a reduced portion of the micron scale beads or spheres are typically successfully bound or held in the discrete sites, which in turn results in many of the available discrete sites remaining unoccupied.
Methods and apparatus for the fluid delivery and removal of micron scale structures that increase the efficiency of such fluid delivery and removal are disclosed.
In one embodiment, the present invention contemplates a method for fluid delivery of micron scale structures comprising providing a silicon or silicon dioxide device that comprises a plurality of wells, wherein each of the wells includes a bottom wall, a side wall, a top opening, and a plurality of protrusions that extend into the interior of the well, delivering a plurality of micron scale structures into the wells using a fluid or a vaporous form thereof, removing the fluid or the vaporous form thereof from the wells, whereby spaces between the protrusions facilitate flow and removal of the fluid or the vaporous form thereof, and allowing the wells with protrusions to retain the plurality of micron scale structures within the wells.
In another embodiment, the present invention contemplates an apparatus that increases the efficiency of fluid delivery of a micron scale structure that includes a silicon or silicon dioxide device that includes a plurality of wells, wherein each of the wells includes a bottom wall, a side wall, a top opening and a plurality of protrusions that extend into the interior of the well. The apparatus achieves this increased efficiency via the protrusions which facilitate flow and removal of the fluid (or its vaporous form), and allowing the wells with protrusions to retain the plurality of micron scale structures within the wells.
In a further embodiment, the present invention contemplates a method for fluid removal of a micron scale structure comprising providing a silicon or silicon dioxide device that has been etched to produce the micron scale structure, wherein the micron scale structure includes a plurality of protrusions extending from the surface thereof, and removing the micron scale structure from the silicon or silicon dioxide device using a fluid, whereby spaces between the protrusions decrease the surface contact area between the micron scale structure and the silicon or silicon dioxide device and facilitate flow of the fluid and removal of the micron scale structure.
In an additional embodiment, the present invention contemplates an apparatus for fluid removal of a micron scale structure comprising a silicon or silicon dioxide device that has been etched to produce the micron scale structure, wherein the micron scale structure includes a plurality of protrusions extending from the surface thereof and whereby spaces between the protrusions decrease the surface contact area between the micron scale structure and the silicon or silicon dioxide device and facilitate flow of a fluid and removal of the micron scale structure using the fluid.
As will be appreciated from the present application, the methodology of the present invention is particularly useful for increasing the efficiency of the fluid delivery and fluid removal of micron scale features in numerous applications. Efficiency is defined as the ratio of the number of devices retained or removed as compared to the number incident.
Preferred and alternative embodiments of the present invention are described in detail below with reference to the following drawings. For purposes of describing embodiments of the present invention, “micron scale structures” refers to a material, device or structure having at least one dimension that ranges in size from about 0.1 micron to about 1000 microns.
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The present invention can be used for fluid delivery of micron scale structures in a wide variety of applications. In one embodiment involving fluid delivery, the micron scale structure is a plurality of micron scale beads or spheres having attached to their surfaces different chemical functional groups or molecules such as a deoxyribonucleic acid (DNA) probes for the analysis of analytes in a sample, and the apparatus for fluid delivery is a silicon device having numerous discrete sites that can bind or hold the micron scale structures to form what is generally known as an array. The array is used for the analysis of analytes, including for example nucleic acid molecules such as DNA molecules and ribonucleic acid (RNA) molecules, in a sample. In this embodiment, the discrete sites of the silicon device are typically micron scale holes having diameters of about 0.1 micron to about 1000 microns, with each silicon device containing about 100,000 to about one million such holes. The silicon device itself can have a multitude of sizes ranging from about 0.1 micron to about 1000 microns. The holes of the silicon device include protrusions which function as described above to facilitate fluid flow and therefore removal of the fluid that is used to deliver the micron scale beads or spheres and, following fluid delivery of the micron scale beads or spheres and removal of the fluid, to retain the micron scale beads or spheres in the holes. The micron scale beads or spheres in this embodiment have diameters of about 0.1 micron to about 1000 microns, with each silicon device incorporating from about 100,000 to about one million such micron scale beads or spheres. Suitable materials for fabrication of the micron scale beads include, for example, plastics, ceramics, glass, polymeric materials such as polystyrene and acrylic polymers and the like. The fluids used for delivery of the micron scale beads or spheres can include various components, including, for example, aqueous buffers, organic solvents, salts and other suitable components. The silicon devices used in this embodiment and having the protrusions as described above can be produced using various well-known techniques, for example, using photolithography masking techniques and subsequent plasma or wet chemical etching.
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The present invention can be used for fluid removal of micron scale structures in a wide variety of applications. In one embodiment of the fluid removal system set forth in
While the preferred embodiments of the invention have been illustrated and described, as noted above, many changes can be made without departing from the spirit and scope of the invention. Accordingly, the scope of the invention is not limited by the disclosure of the preferred embodiment. Instead, the invention should be determined entirely by reference to the claims that follow.