Abstract: Provided is a method for preparing a sample surface for analysis that involves placing a sample surface in droplet-receiving relationship to a reservoir containing an analysis-enhancing fluid. Typically, the analysis-enhancing fluid is comprised of a mass spectrometry matrix material and a carrier fluid, and the carrier fluid is comprised of a low volatility solvent. A droplet of the analysis-enhancing fluid from the reservoir such that the droplet is deposited on the sample surface at a designated site. Such ejection is typically, but not necessarily carried out through the application of focused acoustic energy. Then, the sample is subjected to conditions sufficient to allow the analysis-enhancing fluid to interact with the sample surface to render the sample surface suitable for analysis. Optionally, the sample is analyzed at the selected site. Also provided are systems and devices for preparing a sample surface for analysis.

Abstract: A method is provided for acoustically ejecting from a channel or other container a plurality of fluid droplets, each of which contains one or more particles or other localized volumes. The localized volumes, which can be living cells, are ejected towards sites on a substrate surface, a container, or a channel. An integrated cell sorting and arraying system is also provided that is capable of sorting based upon cellular properties by the selective ejection of cells from a carrier fluid. The cells can be ejected with adjustable velocity and trajectory. The ejected cells can be directed to form an array, wherein each site of the array can contain a single cell. Additionally provided is a method of forming arrays of single live cells more efficiently, rapidly, flexibly, and economically than by other cell array approaches.

Abstract: The present invention provides a method for the acoustic ejection of fluid droplets from fluid-containing reservoirs to form arrays suitable for high-throughput combinatorial crystallization experiments. Such arrays may utilize very small fluid volumes, in the order of picoliters. The method is especially suited to preparing combinatorial libraries useful in developing techniques for crystallizing biomacromolecules, such as proteins. The small volumes conserve macromolecules that may be costly and rare, and permit the testing of a large number of experimental crystallization conditions for a given amount of a macromolecule. The time required for the experiments may be very short due to the small volumes. The invention is conducive to forming high-density microarrays of small volume crystallization experiments. Acoustic detection of crystals in situ, and distinction between biomacromolecular and non-biomacromolecular crystals, are also taught.

Abstract: The invention relates to a method and system for acoustically depositing a fluid on a surface of a cell sample. A reservoir containing a fluid is provided, and the cell sample surface is positioned in droplet-receiving relationship to the reservoir. Once the reservoir and the cell sample surface are appropriately positioned, focused acoustic energy is applied to eject a droplet of the fluid from the reservoir. As a result, the droplet is deposited on the sample surface at a designated site. Optionally, the fluid may be an analysis-enhancing fluid that contains a label moiety or a mass-spectrometry matrix material. When an analysis-enhancing fluid is used, the sample is typically subjected to conditions effective to allow the analysis-enhancing fluid to interact with the sample surface so as to render the sample surface suitable for analysis. Then, the sample may be analyzed at the designated site.

Abstract: Partially nonhybridizing oligonucleotides are provided that contain two or more hybridizing segments, with any two hybridizing segments separated by a nonhybridizing spacer segment, i.e., a nucleotidic or nonnucleotidic segment that has little or no likelihood of binding to an oligonucleotide sequence found in nature. Oligonucleotide arrays are also provided in which at least one of the oligonucleotides of the array is a partially nonhybridizing oligonucleotide. The partially nonhybridizing oligonucleotides serve as multifunctional probes wherein each hybridizing segment of a single partially nonhybridizing oligonucleotide serves as an individual probe. Also provided are methods for preparing and using the partially nonhybridizing oligonucleotides and arrays formed therewith. A particularly preferred method of array fabrication involves the use of focused acoustic energy.

Abstract: The present invention provides a method and device for the acoustic ejection of fluid droplets from each of a plurality of fluid-containing reservoirs. The droplets are ejected toward sites on a substrate surface for deposition thereon. The device is comprised of: a plurality of reservoirs each adapted to contain a fluid; an ejector comprising a means for generating acoustic radiation and a means for focusing the generated acoustic radiation so as to eject fluid droplets from the reservoir fluids; and a means for positioning the ejector in acoustically coupled relationship to each of the reservoirs. The invention is useful in a number of contexts, particularly in the preparation of biomolecular arrays.

Abstract: The present invention provides a unique and highly accurate method for generating molecular arrays of very high density on porous surfaces. The method involves the application of focused acoustic energy to each of a plurality of fluid-containing reservoirs to eject a small fluid droplet—on the order of 1 picoliter or less—from each reservoir to a site on a porous substrate surface. High density molecular arrays are provided as well, in which greater than about 62,500 molecular moieties, serving as array elements, are present on a porous surface. Biomolecular arrays that can be generated using focused acoustic ejection include oligonucleotide arrays and peptidic arrays.

Abstract: The invention relates to the efficient transport of a small volume of fluid, such as may be required by mass spectrometers and other devices configured to process and/or analyze small samples of biomolecular fluids. Such transport involves nozzleless acoustic ejection. In some instances, sample molecules contained in droplets of fluid are introduced from a reservoir into an ionization chamber of an analytical device. In other instances, sample molecules are introduced into a small capillary by directing focused acoustic radiation at a focal point near the surface of a fluid sample. In still other instances, acoustic ejection is used to form an array on a surface, wherein the features of the array are ionized for analysis. The invention may be used with microfluidic devices. Thus, the invention facilitates the processing and/or analysis of various types of samples, such as biomolecules having high molecular weights.

Abstract: A method for selectively depositing analysis-enhancing fluid on a sample surface is disclosed. The method involves providing a sample having a surface that exhibits variations in a surface characteristic that corresponds to desirability for receiving an analysis-enhancing fluid. Once a site on the sample surface is selected according to the surface characteristic at the site, focused radiation, typically acoustic radiation, is applied in a manner effective to eject a droplet of the analysis-enhancing fluid from a reservoir. As a result, the droplet is deposited on the sample surface at the selected site. Optionally, the sample at the selected site is analyzed. Systems for selectively depositing analysis-enhancing fluids are also disclosed.

Abstract: The present invention provides a method and device for the acoustic ejection of fluid droplets from each of a plurality of fluid-containing reservoirs. The droplets are ejected toward sites on a substrate surface for deposition thereon. The device is comprised of: a plurality of reservoirs each adapted to contain a fluid; an ejector comprising a means for generating acoustic radiation and a means for focusing the generated acoustic radiation so as to eject fluid droplets from the reservoir fluids; and a means for positioning the ejector in acoustically coupled relationship to each of the reservoirs. The invention is useful in a number of contexts, particularly in the preparation of biomolecular arrays.

Abstract: The invention provides a method for generating droplets. Extremely fine droplets may be generated (on the order of 1 picoliter or less) using focused acoustic energy to eject the droplets from a reservoir containing two or more immiscible fluids. The droplets may include immiscible fluids or a single fluid. Typically, the droplets are ejected onto discrete sites on a substrate surface so as to form an array thereon. In some instances, the reservoirs contain layers of immiscible fluids, wherein an upper layer exhibits a nonuniform thickness. In such a case, fluid from a lower fluid layer may be propelled through an aperture region of the upper layer.

Abstract: The present invention provides a method for the acoustic ejection of fluid droplets from each of a plurality of fluid-containing reservoirs to prepare combinatorial libraries in the form of microarrays. An acoustic ejection device is used comprised of a plurality of fluid reservoirs, an ejector for generating acoustic radiation and focusing the acoustic radiation generated at a focal point sufficiently near the fluid surface in each of the reservoirs such that a fluid droplet is ejected therefrom toward a site on a substrate surface, and a device for positioning the ejector in acoustically coupled relationship to each of the reservoirs. The combinatorial libraries may comprise biological or nonbiological moieties.

Abstract: A method and device for generating solid particles using focused acoustic energy are provided. A solution of a compound of interest is provided in a solvent, which may be an aqueous fluid, a nonaqueous fluid, or a supercritical fluid. Focused acoustic energy is used to eject a droplet of the solution, which is then directed into or through an antisolvent that upon admixture with the solution droplet causes the compound in the droplet to precipitate. In a preferred embodiment, the solvent is an aqueous or organic liquid, and the antisolvent is a supercritical fluid.

Abstract: The invention relates to the efficient transport of a small fluid sample such as that may be required by analytical devices such as mass spectrometers configured to analyze small samples of biomolecular fluids. Such transport involves nozzleless acoustic ejection, wherein analyte molecules are introduced from a reservoir holding a fluid into an ionization chamber of an analytical device or a small capillary by directing focused acoustic radiation at a focal point near the surface of the fluid sample. This facilitates the analysis of various types of analytes such as biomolecular analytes having a high molecular weight.

Abstract: A method and device for generating pharmaceutical agent particles using focused acoustic energy are provided. A solution of the pharmaceutical agent is provided in a solvent, which may be an aqueous fluid, a nonaqueous fluid, or a supercritical fluid. Focused acoustic energy is used to eject a droplet of the solution, which is then directed into or through an antisolvent that upon admixture with the solution droplet causes the pharmaceutical agent in the droplet to precipitate. In a preferred embodiment, the solvent is an aqueous or organic liquid, and the antisolvent is a supercritical fluid.

Abstract: A method and device for generating droplets of immiscible fluids are provided. Extremely fine droplets may be generated, on the order of 1 picoliter or less, using focused acoustic energy to eject the droplets from a reservoir containing two or more immiscible fluids. Optionally, the droplets may be ejected onto discrete sites on a substrate surface so as to form an array thereon.

Abstract: The present invention provides a method and device for the acoustic ejection of fluid droplets from fluid-containing reservoirs using focusing means having an F-number greater than approximately 2. The droplets are ejected toward designated sites on a substrate surface for deposition thereon. In one embodiment, the device is comprised of: a plurality of reservoirs each adapted to contain a fluid; an ejector comprising a means for generating acoustic radiation and a large F-numbered means for focusing the acoustic radiation at a focal point near the fluid surface in each of the reservoirs; and a means for positioning the ejector in acoustically coupled relationship to each of the reservoirs. The invention is useful in a number of contexts, particularly in the preparation of biomolecular arrays.