Abstract: The present invention provides a method for the acoustic ejection of fluid droplets from fluid-containing reservoirs to form small volumes high throughput combinatorial experimentation for crystallization. The method is especially suited to preparing combinatorial libraries of small volume crystallization experiments for crystallizing difficult to crystallize biomacromolecules. The small volumes conserve costly and difficult to obtain macromolecules and permit an increased number of experimental crystallization conditions tested for an amount of the biomacromolecule of interest for crystallization. The time required for the experiments is greatly reduced by the scaled down experimental 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 is also taught.

Abstract: An acoustic ink printing device ejects droplets of at least one fluid onto a printing medium. The acoustic ink printing device includes at least one printing means for ejecting a respective one of the fluids. Each printing means includes at least one ejector, associated with at least one pixel on the printing medium, and a means for generating an acoustic wave to eject respective droplets from the ejectors to the respective pixels. A processor, electrically connected to each of the printing means, minimizes a number of scans each of the printheads makes over a current swath of the printing medium.

Abstract: Methods and devices are disclosed that use focused acoustic energy to generate solid particles containing at least one compound of interest. Focused acoustic radiation serves to eject droplets containing a compound of interest dissolved in a solvent. The droplets are subjected to a condition that allows for the compound of interest to precipitate out of solution, thereby generating solid particles. The particles are typically of controlled size, composition, and/or structure. Often, particles of substantially identical size are generated.

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 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: An active controller is provided to control operation of an acoustic printhead in which impedance of the printhead changes with both the active printing row and the distribution of active ejectors in the row. The active controller varies the input power to the printhead in response to active ejectors. Power requirements are insured while also reducing power consumption and maintaining print quality. The determination of RF power is based on the active row, how many ink ejectors are to be switched on, and their position within a row. Look-up tables used to determine proper attenuation or power values are provided in a cascaded fashion.

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: A printhead for an acoustic ink printer includes at least one acoustic generator for producing acoustic sound waves. The printhead also includes at least one lens. Each lens corresponds to one of the acoustic generators. A fluid is positioned over the at least one lens. A cover is positioned over the fluid. The cover includes at least one aperture. Each of the apertures corresponds to one of the lenses. An edge portion of each aperture contacts the fluid, thereby forming a corresponding meniscus in the fluid. Each lens focuses the acoustic sound waves produced by the respective acoustic generator to an ejection point on the corresponding meniscus. A droplet of the fluid is ejected from each of the ejection points. Directions of each of the acoustic sound waves are at respective oblique angles with respect to the corresponding meniscus. A direction at which each droplet is ejected from each ejection point is a function of a duration of the acoustic sound wave generated by the acoustic generator.

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: A printhead for an acoustic ink printer includes at least one acoustic generator for producing acoustic sound waves. The printhead also includes at least one lens. Each lens corresponds to one of the acoustic generators. A fluid is positioned over the at least one lens. A cover is positioned over the fluid. The cover includes at least one aperture. Each of the apertures corresponds to one of the lenses. An edge portion of each aperture contacts the fluid, thereby forming a corresponding meniscus in the fluid. Each lens focuses the acoustic sound waves produced by the respective acoustic generator to an ejection point on the corresponding meniscus. A droplet of the fluid is ejected from each of the ejection points. Directions of each of the acoustic sound waves are at respective oblique angles with respect to the corresponding meniscus. A direction at which each droplet is ejected from each ejection point is a function of a duration of the acoustic sound wave generated by the acoustic generator.

Abstract: An image forming system is provided having a printhead including a plurality of ejectors arranged in one or more sequenced groups. Each of the ejectors has a sequence number assigned thereto, ranging from a minimum value and incremented to a maximum value within each sequence group. The plurality of ejectors have an arrangement such that a difference between the sequence number assignment of any two adjacent ejectors is less than a difference between the maximum and minimum sequence number assignment values.

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: An apparatus and method for ink-jet printing on a recording medium is provided which includes the steps of jetting aqueous ink drops on paper in the form of an image. The aqueous ink used is a slow-drying (high-surface tension) ink which does not penetrate the paper/paper fibers for a relatively long time. Prior to penetration of the paper/paper fibers, the water in the droplet is quickly evaporated from the ink while still resident on the paper surface. The evaporation process is substantially completed prior to an additional liquid ink being jetted onto the same or adjoining location of the recording medium. The evaporation is rapid enough to prevent the resident ink from substantially migrating/wicking to any adjacent location or into the recording medium. Further the drying energy is transferred to the resident ink spots from the same direction as the printheads ensuring less energy requirement.

Abstract: An apparatus for ink-jet printing on a recording medium is provided which includes the steps of jetting aqueous ink drops on paper in the form of an image. The aqueous ink used is a slow-drying (high-surface tension) ink which does not penetrate the paper/paper fibers for a relatively long time. Prior to penetration of the paper/paper fibers, the water in the droplet is quickly evaporated from the ink while still resident on the paper surface. The evaporation process is substantially completed prior to an additional liquid ink being jetted onto the same or adjoining location of the recording medium. The evaporation is rapid enough to prevent the resident ink from substantially migrating/wicking to any adjacent location or into the recording medium. Further the drying energy is transferred to the resident ink spots from the same direction as the printheads ensuring less energy requirement.

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 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.

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.