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: 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: This invention is directed to the use of focused energy, particularly focused acoustic energy, in the spatially directed ejection of cells suspended in a carrier fluid, e.g., for providing a pattern of cells on a substrate surface, such as a cellular array.

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: 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: The invention provides a device comprising a substrate having a plurality of different molecular probes attached to a surface thereof and an integrated indicator that exhibits a response when exposed to a condition to which the substrate may be exposed. Each different molecular probe is selected to interact with a different corresponding target, and the indicator response is detectable after removing the indicator from the condition. Alternatively, a substrate is provided having a plurality of molecular probes attached to a surface thereof and a plurality of different integrated indicators. Each indicator is selected to exhibit a response when exposed to one of a plurality of conditions to which the substrate may be exposed. The inventive devices are typically used for biomolecular, or more specifically, nucleotidic assays. The invention also provides for various apparatuses and methods for assaying a sample using the inventive devices.

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 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 means for positioning the ejector in acoustically coupled relationship to each of the reservoirs. The combinatorial libraries may comprise biological or nonbiological moieties.

Abstract: The invention provides a device comprising a substrate having a plurality of different molecular probes attached to a surface thereof and an integrated indicator that exhibits a response when exposed to a condition to which the substrate may be exposed. Each different molecular probe is selected to interact with a different corresponding target, and the indicator response is detectable after removing the indicator from the condition. Alternatively, a substrate is provided having a plurality of molecular probes attached to a surface thereof and a plurality of different integrated indicators. Each indicator is selected to exhibit a response when exposed to one of a plurality of conditions to which the substrate may be exposed. The inventive devices are typically used for biomolecular, or more specifically, nucleotidic assays. The invention also provides for various apparatuses and methods for assaying a sample using the inventive devices.

Abstract: The invention provides a device comprising a substrate having a surface capable of attaching a plurality of molecular moieties, or a surface having a plurality of molecular moieties attached thereto. The substrate also contains machine-readable information relating to the molecular moieties. The information may be contained in a discrete region of the substrate that is non-coplanar with respect to the substrate surface having the plurality of molecular moieties attached thereto. The information may, for example, relate to the identity of the attached molecular moieties or to instructions for attaching the molecular moieties. Also provided are methods and machines for forming and using the devices.

Abstract: A method is provided for acoustically ejecting from a container that is preferably a channel, a plurality of particles or localized volumes that can be single living cells contained in fluid droplets toward sites on a substrate surface or alternatively or in addition thereto into containers or channels for deposition at a target array site or a container or channel by acoustic ejection. An integrated cell sorting and arraying system also is provided that is capable of selective sorting, into channels or other containers substantially transected by a common plane, parallel to a surface of the fluid, transecting the container from which cells are ejected by selective ejection of cells with adjustable velocity parallel to the fluid surface, and simultaneously selectively forming an array of cells on a substrate surface comprising an array of substantially planar sites is provided, wherein each site contains a single cell.

Abstract: This invention is directed to the use of focused acoustic energy in the spatially directed ejection of cells suspended in a carrier fluid, for printing and patterning cells onto a substrate surface, for example to pattern an array of cells onto a substrate. An array of cells on a substrate surface comprising an array of substantially planar sites, with each site containing a single cell, is consequently also provided. Also disclosed are methods for the systematic generation and screening of arrays of living cells on a substrate from fluids containing one or more living cells. A method of attaching cells displaying a specific marker moiety on their surface, through specific recognition of the marker moiety by a cognate moiety that is linked to the surface is provided. Cells may be transformed to display a specific marker recognized by a corresponding cognate moiety, or the marker moiety may appear on untransformed cells.

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 means for positioning the ejector in acoustically coupled relationship to each of the reservoirs. The combinatorial libraries may comprise biological or nonbiological moieties.

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 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 combinatorial libraries may comprise biological or nonbiological moieties.

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 relates to arrays of peptidic molecules and the preparation of peptide arrays using focused acoustic energy. The arrays are prepared by acoustically ejecting peptide-containing fluid droplets from individual reservoirs towards designated sites on a substrate for attachment thereto.

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: 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.