Abstract: Devices and methods are provided for ejecting a droplet from a reservoir using focused acoustic radiation having a plurality of nonsimultaneous and discrete frequency ranges. Such frequency ranges may be used to control droplet volume and/or velocity. Optionally, satellite fluid ejection from the reservoir is suppressed.

Abstract: Devices and methods are provided for ejecting a droplet from a reservoir using focused acoustic radiation having a plurality of nonsimultaneous and discrete frequency ranges. Such frequency ranges may be used to control droplet volume and/or velocity. Optionally, satellite fluid ejection from the reservoir is suppressed.

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: Method and system for monitoring for a change in the amount and/or concentration of a pathogen in a pathogenic fluid. The method includes providing a pathogen-impermeable enclosure enclosing the pathogenic fluid, wherein the pathogenic fluid includes a pathogen and a carrier fluid. Additionally, the method includes acoustically monitoring for a change in the amount and/or concentration of the pathogen enclosed in the pathogen-impermeable enclosure.

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: Compounds useful as protease inhibitors are provided, as are methods of use and preparation of such compounds and compositions containing such compounds. In one embodiment, the compounds are useful for inhibiting HIV protease enzymes, and are therefore useful in slowing the proliferation of HIV.

Abstract: Compounds useful as protease inhibitors are provided, as are methods of use and preparation of such compounds and compositions containing such compounds. In one embodiment, the compounds are useful for inhibiting HIV protease enzymes, and are therefore useful in slowing the proliferation of HIV.

Abstract: Compounds useful as antimicrobials are provided, as are methods of use and preparation of such compounds and compositions containing such compounds. In one embodiment, the compounds are derivatives having a carbapenem core, and are useful for treating a microorganism infection.

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: 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: 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: In an embodiment of the invention, a method of enhancing the efficacy of an anti-infective therapeutic agent against an obligate or facultative intracellular parasite in a host is provided. The method comprises administering to the host an effective amount of a bifunctional compound of less than about 5000 Daltons comprising the therapeutic or an active derivative, fragment or analog thereof and a protein binding moiety. The protein binding moiety binds to at least one intracellular protein. The bifunctional compound has a higher intracellular concentration as compared to the therapeutic itself in order to enhance the efficacy of the anti-infective therapeutic against the obligate or facultative intracellular parasite.

Abstract: A method for modulating at least one pharmacokinetic property of a drug which degrades mRNA upon administration to a host by an siRNA mechanism is provided. In a further embodiment of this invention, a bifunctional compound comprising an siRNA and a recruiter moiety are provided. The recruiter moiety may be lipophilic and may enable the siRNA to cross cell membranes and then targets an endogenous, intracellular protein to allow better distribution of the therapeutic into the cell and therefore, higher efficacy.

Abstract: A method is provided for improving at least one pharmacokinetic property and maintaining or improving affinity of a therapeutic upon administration to a host. In the method, one administers to the host an effective amount of a bifunctional compound of less than about 5000 Daltons comprising the therapeutic or an active derivative, fragment or analog thereof and a recruiter ligand moiety. The recruiter ligand moiety binds to at least one biomoiety. The bifunctional compound has at least one modulated pharmacokinetic property upon administration to the host and equivalent or greater affinity for a target of the therapeutic as compared to a free drug control that comprises the therapeutic. In addition, the overall drug efficacy is improved by the steric bulk of the bifunctional complexed with the recruited biomoiety.

Abstract: A method for modulating at least one pharmacokinetic property of an anti-angiogenic or blood disease or steroid therapeutic and efficacy upon administration to a host is provided. One administers to the host an effective amount of a bifunctional compound of less than about 5000 Daltons comprising the anti-angiogenic or blood disease or steroid therapeutic or an active derivative thereof and a pharmacokinetic modulating moiety. The pharmacokinetic modulating moiety binds to at least one intracellular protein. The bifunctional compound has at least one modulated pharmacokinetic property upon administration to the host as compared to a free drug control that comprises the anticancer therapeutic as well as enhanced efficacy not due to compound degradation. It is preferred that the pharmacokinetic modulating moiety has a mass of less than 1100 Daltons.

Abstract: Devices and methods are provided for reducing the uncontrolled electrostatic charges that can alter the volume and/or trajectory of a droplet, which is typically ejected through the application of focused acoustic radiation. Also provided are reservoirs and substrates, e.g., well plates formed from a material that is at least partially nonmetallic or polymeric and either has an electrical resistivity of no more than about 1011 ohm-cm, has a surface electrical resistivity of no more than about 1012 ohm/sq, or both.

Abstract: A method for modulating at least one pharmacokinetic property of a protease inhibitor upon administration to a host is provided. One administers to the host an effective amount of a bifunctional compound of less than about 5000 daltons comprising the protease inhibitor or an active derivative thereof and a pharmacokinetic modulating moiety. The pharmacokinetic modulating moiety binds to at least one intracellular protein. The bifunctional compound has at least one modulated pharmacokinetic property upon administration to the host as compared to a free drug control that comprises the protease inhibitor.

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: This invention is directed to the use of focused energy, particularly focused acoustic energy, in the spatially directed ejection of circumscribed volumes of a fluid which differ in acoustic impedance from the surrounding fluid.

Abstract: Provided is a method of transporting fluid which involves acoustic ejection into a small opening. The opening may be, for example, the inlet opening of a sample vessel. Alternatively, it may be an opening in a microfluidic device. The ejection is typically, but not necessarily carried out through the application of focused acoustic energy. The fluid being transported typically comprises a moiety of interest for analysis or further processing, which may be a biomolecule. The volumes of transported fluid may be in the nanoliter or picoliter range. Ejection may occur from very small volumes and the ejected droplet may carry away a significant fraction of the volume from which ejection occurs.