Abstract: Methods are provided for analyzing characteristics of fluids in the context of an acoustic ejection system. Such a system has a controller, an acoustic radiation generator, and a coupling medium coupling the radiation to a reservoir holding fluid. The methods can use acoustic radiation to both perturb a surface of the fluid in the reservoir and analyze the effect of the perturbation. The methods may use information about prior fluids. The methods of the invention can determine physical characteristics such as speed of sound and viscosity. The methods also include ways to determine a level of acoustic energy suitable to eject a droplet. Preferably the methods are executed automatically under control of programming of a controller of an acoustic ejection system.

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 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: 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 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 reservoirs in acoustically coupled relationship to the ejector. The invention is useful in a number of contexts, particularly in the preparation of biomolecular arrays.

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 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: 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 present invention provides a method and device for the acoustic ejection of fluid droplets having a constant drop size from fluid-containing reservoirs having varying fluid heights contained therein without the need for repositioning the acoustic ejector in the z direction by adjusting the RF frequency and amplitude. 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, means for controlling the RF frequency and amplitude used to generate the acoustic radiation, 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: 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: 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 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 reservoirs in acoustically coupled relationship to the ejector. 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 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 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 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 present invention provides a method and device for the acoustic ejection of fluid droplets having a constant drop size from fluid-containing reservoirs having varying fluid heights contained therein without the need for repositioning the acoustic ejector in the z direction by adjusting the RF frequency and amplitude. 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, means for controlling the RF frequency and amplitude used to generate the acoustic radiation, 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.