Focused acoustic ejection cell sorting system and method
First Claim
1. A separation method comprising the steps:
- (a) detecting in a fluid having a surface and a plurality of localized volumes having a different acoustic impedance than the fluid a single localized volume located sufficiently near the surface for ejection;
(b) determining whether the single localized volume possesses one or more properties;
(c) selecting the single localized volume for ejection from the fluid based on the determination of one or more properties in step (b);
and (d) ejecting the single localized volume from the fluid by use of focused energy.
1 Assignment
0 Petitions
Accused Products
Abstract
A method is provided for acoustically ejecting from a container that is preferably a channel, a plurality of particles or localized volumes that can be single living cells contained in fluid droplets toward sites on a substrate surface or alternatively or in addition thereto into containers or channels for deposition at a target array site or a container or channel by acoustic ejection. An integrated cell sorting and arraying system also is provided that is capable of selective sorting, into channels or other containers substantially transected by a common plane, parallel to a surface of the fluid, transecting the container from which cells are ejected by selective ejection of cells with adjustable velocity parallel to the fluid surface, and simultaneously selectively forming an array of cells on a substrate surface comprising an array of substantially planar sites is provided, wherein each site contains 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, while permitting efficient, continuous and simultaneous sorting of cells based upon selection by measurement of detectible properties quantitatively or semiquantitatively, and multiple ejection target selections permitting non-binary or severally branched decision making. An integrated system and methods are also provided for ejection of selected particles or circumscribed volumes such as live cells from a continuous stream of particles or circumscribed volumes flowing in fluidic ejection channels into flowing fluidic target channels based upon selection by measurement of detectible properties quantitatively or semiquantitatively, and multiple ejection target selections permitting non-binary or severally branched decision making integrated with the measurement by way of a processor.
101 Citations
66 Claims
-
1. A separation method comprising the steps:
-
(a) detecting in a fluid having a surface and a plurality of localized volumes having a different acoustic impedance than the fluid a single localized volume located sufficiently near the surface for ejection;
(b) determining whether the single localized volume possesses one or more properties;
(c) selecting the single localized volume for ejection from the fluid based on the determination of one or more properties in step (b);
and(d) ejecting the single localized volume from the fluid by use of focused energy. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 28, 29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40)
-
-
16. A system for the separation, from a carrier fluid having a fluid surface and containing a plurality of circumscribed volumes having a different acoustic impedance than the carrier fluid, of one or more of the circumscribed volumes, the system comprising:
-
a fluidic container;
a detector for detecting the localized volume and determining a property of the localized volume; and
an acoustic ejector of fluid droplets from the carrier fluid, comprising an acoustic radiation generator for generating acoustic radiation and a focusing means for focusing the acoustic radiation at a focal point near the fluid surface;
wherein the circumscribed volumes present in the carrier fluid that are detected to be sufficiently near the fluid surface for ejection may be acoustically ejected to a target from the carrier fluid in a fluid droplet depending upon whether the circumscribed volume possesses one or more properties.
-
-
27. A system for the separation, from a carrier fluid having a surface containing a plurality of circumscribed volumes having a different acoustic impedance than the carrier fluid, of one or more of the circumscribed volumes, the system comprising:
-
a container;
a substrate having a substrate surface oriented substantially parallel to the surface;
means for acoustically ejecting from the carrier fluid through the aperture onto a location on the substrate surface a circumscribed volume having a different acoustic impedance than the carrier fluid, wherein the circumscribed volume present in the carrier fluid that is detected near the fluid surface below the aperture may be acoustically ejected from the carrier fluid onto a substrate location in a fluid droplet depending upon whether the localized volume possesses one or more properties.
-
-
37. A method for ejecting one or more cells from a colony of cells disposed on a medium surface to a target comprising a substrate surface or a container, the method comprising locating a colony and ejecting the cells by focused energy.
-
41. A system for ejecting cells from a colony of cells disposed on a surface of a medium having a bulk, comprising:
-
an acoustic energy source;
means for focusing acoustic energy from said acoustic energy source to a focal point;
means for positioning the focal point at any point in the medium or the colony of cells, wherein the cells are ejected by delivering acoustic energy to the focal point with an adequate power and for a sufficient time to deliver a quantity of acoustic energy that ejects the cells. - View Dependent Claims (42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 58, 59, 60, 61)
-
-
57. A method for conditioning a material to facilitate subsequent acoustic ejection in a delineated volume of material comprising delivering acoustic energy to a focal point in the material.
- 62. A method for delivering thermal energy to a delineated volume of material comprising delivering acoustic energy to a focal point in the material.
Specification