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: 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: The invention relates to methods and devices that use focused radiation to handle and/or monitor pathogenic fluids. In particular, a method is provided for dispensing one or more droplets of a fluid containing a pathogen. The method involves providing the pathogen-containing fluid in a reservoir and applying focused radiation to the pathogen-containing fluid in the reservoir in a manner effective to eject a droplet of the fluid therefrom. Often, a pathogen-impermeable enclosure is used.

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 device for controlling the composition and/or volume of a fluid within a reservoir. The device includes a reservoir adapted to contain at least one fluid, a means for monitoring a characteristic of the fluid contained in the reservoir, and a means for introducing additional fluid into the reservoir according to the fluid characteristic monitored by the monitoring means. The device also includes an acoustic generator for generating acoustic radiation. A dispensing means may be provided as well. Other devices and methods that use acoustic radiation to control the composition and/or volume of a fluid within a reservoir are included.

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: The invention provides devices and methods for acoustically assessing the contents of a plurality of reservoirs that are typically provided as an array. An acoustic radiation generator is employed for generating acoustic radiation having an image field of a size sufficient to interrogate a plurality of selected reservoirs at one time. The generator is placed in acoustic coupling relationship via a fluid acoustic coupling medium to the selected reservoirs, and acoustic radiation generated by the generator is transmitted through the coupling medium, an exterior surface of the selected reservoirs, and the selected reservoirs. A characteristic of the transmitted acoustic radiation is analyzed so as to assess the contents of each of the selected reservoirs. Fluid may be ejected from the selected reservoirs according to the assessment. Optionally, a means is provided for removing fluid acoustic coupling medium from the exterior surface after acoustic assessment.

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 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: 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 provides devices and methods for acoustically assessing the contents in a plurality of reservoirs. Each reservoir has a portion adapted to contain a fluid, and an acoustic radiation generator is positioned in acoustic coupling relationship to each of the reservoirs. Acoustic radiation generated by the acoustic radiation generator is transmitted through at least the portion of each reservoir to an analyzer. The analyzer is capable of analyzing a characteristic of the transmitted acoustic radiation and optionally correlating the characteristic to a property of the reservoirs' contents. The invention is particularly suited for assessing the contents of a plurality of reservoirs to allow for accuracy and control over the dispensing of fluids therefrom.

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 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 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 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: 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.