Picoliter Inc.

Labcyte Inc.

Other

Scios Inc.

Mitchell Wayne Mutz

Richard N Ellson

James K Foote

Richard G Stearns

David Soong-Hua Lee

Richard Caprioli

George McLendon

John P Cooke

Barbara Cordell

Shehrzad Ahmed Qureshi

Robert F Balint

Jeffrey N Higaki

David Soon-Hua Lee

Richard M Caprioli

George Mclendon

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.

Droplet ejection using focused acoustic radiation having a plurality of frequency ranges

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. The acoustically monitoring for a change in the amount and/or concentration of the pathogen enclosed in the pathogen-impermeable enclosure includes generating acoustic radiation directed towards the pathogen-impermeable enclosure, transmitting the acoustic radiation through the pathogen-impermeable enclosure or reflecting the acoustic radiation by the pathogenic fluid, receiving the acoustic radiation transmitted through the pathogen-impermeable enclosure or receiving the acoustic radiation reflected by the pathogenic fluid, and analyzing the received acoustic radiation.

Acoustic radiation for ejecting and monitoring pathogenic fluids

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.

Acoustic assessment of characteristics of a fluid relevant to acoustic ejection

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.

Acoustic assessment of fluids in a plurality of reservoirs

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.

Peptide arrays and methods of preparation

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 10ohm-cm, has a surface electrical resistivity of no more than about 10ohm/sq, or both.

Droplet dispensation from a reservoir with reduction in uncontrolled electrostatic charge

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.

Apparatus for acoustic ejection of circumscribed volumes from a fluid

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.

Acoustic ejection into small openings

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.

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. This method permits efficient, continuous, and simultaneous sorting of cells based upon the quantitative or semiquantitative measurement of cellular properties, and also permits non-binary or severally-branched decision-making. An integrated system, which includes a processor, and methods are also provided for the detection, selection, and ejection of selected particles or circumscribed volumes, such as live cells, from a continuous stream of fluid-suspended particles or other circumscribed volumes flowing in channels.

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Palo Alto, CA, United States of America

Mitchell Wayne Mutz