Keunho Ahn

US Patent:

20050221339, Oct 6, 2005

Filed:

Oct 12, 2004

Appl. No.:

10/963044

Inventors:

Andrew Griffiths - Cambridge, GB
David Weitz - Bolton MA, US
Darren Link - Guilford CT, US
Keunho Ahn - Boston MA, US
Jerome Bibette - Paris, FR

International Classification:

C12Q001/68
G01N033/53
G01N033/555

US Classification:

435006000, 435007100, 436522000

Abstract:

The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalising the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

US Patent:

20060078888, Apr 13, 2006

Filed:

Oct 8, 2004

Appl. No.:

10/961695

Inventors:

Andrew Griffiths - Cambridge, GB
David Weitz - Bolton MA, US
Darren Link - Guilford CT, US
Keunho Ahn - Boston MA, US
Jerome Bibette - Paris, FR

International Classification:

C12Q 1/68

US Classification:

435006000

Abstract:

The invention describes a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; and (b) sorting the genetic elements which express the gene product having the desired activity; wherein at least one step is under microfluidic control. The invention enables the in vitro evolution of nucleic acids and proteins by repeated mutagenesis and iterative applications of the method of the invention.

US Patent:

20060078893, Apr 13, 2006

Filed:

Oct 12, 2004

Appl. No.:

10/962952

Inventors:

Andrew Griffiths - Cambridge, GB
David Weitz - Bolton MA, US
Darren Link - Guilford CT, US
Keunho Ahn - Boston MA, US
Jerome Bibette - Paris, FR

International Classification:

C40B 40/08
C40B 40/10
C40B 50/04

US Classification:

435006000, 435007100

Abstract:

The invention describes a method for the synthesis of compounds comprising the steps of: (a) compartmentalising two or more sets of primary compounds into microcapsules; such that a proportion of the microcapsules contains two or more compounds; and (b) forming secondary compounds in the microcapsules by chemical reactions between primary compounds from different sets; wherein one or both of steps (a) and (b) is performed under microfluidic control; preferably electronic microfluidic control The invention further allows for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, and which is co-compartmentalised into the microcapsules.

US Patent:

20070003442, Jan 4, 2007

Filed:

Feb 23, 2006

Appl. No.:

11/360845

Inventors:

Darren Link - Guilford CT, US
David Weitz - Bolton MA, US
Galder Cristobal-Azkarate - Arrasate-Mondragon, ES
Zhengdong Cheng - College Station TX, US
Keunho Ahn - Boston MA, US

Assignee:

President and Fellows of Harvard College - Cambridge MA

International Classification:

B01L 3/00

US Classification:

422099000

Abstract:

Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one aspect, the invention relates to systems and methods for making droplets of fluid surrounded by a liquid, using, for example, electric fields, mechanical alterations, the addition of an intervening fluid, etc. In some cases, the droplets may each have a substantially uniform number of entities therein. For example, 95% or more of the droplets may each contain the same number of entities of a particular species. In another aspect, the invention relates to systems and methods for dividing a fluidic droplet into two droplets, for example, through charge and/or dipole interactions with an electric field. The invention also relates to systems and methods for fusing droplets according to another aspect of the invention, for example, through charge and/or dipole interactions. In some cases, the fusion of the droplets may initiate or determine a reaction. In a related aspect of the invention, systems and methods for allowing fluid mixing within droplets to occur are also provided. In still another aspect, the invention relates to systems and methods for sorting droplets, e.g., by causing droplets to move to certain regions within a fluidic system. Examples include using electrical interactions (e.g., charges, dipoles, etc.) or mechanical systems (e.g., fluid displacement) to sort the droplets. In some cases, the fluidic droplets can be sorted at relatively high rates, e.g., at about 10 droplets per second or more. Another aspect of the invention provides the ability to determine droplets, or a component thereof, for example, using fluorescence and/or other optical techniques (e.g., microscopy), or electric sensing techniques such as dielectric sensing.

US Patent:

20070092914, Apr 26, 2007

Filed:

Dec 4, 2006

Appl. No.:

11/633849

Inventors:

Andrew Griffiths - Cambridge, GB
David Weitz - Bolton MA, US
Darren Link - Guilford CT, US
Keunho Ahn - Boston MA, US
Jerome Bibette - Paris, FR

International Classification:

C40B 40/04

US Classification:

435007100

Abstract:

The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalising the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

US Patent:

20070184489, Aug 9, 2007

Filed:

Dec 20, 2006

Appl. No.:

11/643151

Inventors:

Andrew Griffiths - Cambridge, GB
David Weitz - Bolton MA, US
Darren Link - Guilford CT, US
Keunho Ahn - Boston MA, US
Jerome Bibette - Paris, FR

International Classification:

C40B 30/06
C40B 40/10
C40B 40/04

US Classification:

435007100

Abstract:

The invention describes a method for the synthesis of compounds comprising the steps of: (a) compartmentalising two or more sets of primary compounds into microcapsules; such that a proportion of the microcapsules contains two or more compounds; and (b) forming secondary compounds in the microcapsules by chemical reactions between primary compounds from different sets; wherein one or both of steps (a) and (b) is performed under microfluidic control; preferably electronic microfluidic control The invention further allows for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, and which is co-compartmentalised into the microcapsules.

US Patent:

20070195127, Aug 23, 2007

Filed:

Jan 24, 2007

Appl. No.:

11/698298

Inventors:

Keunho Ahn - San Diego CA, US
Henry Chong - Cambridge MA, US
Jeremy Agresti - Cambridge MA, US
David Weitz - Bolton MA, US
Darren Link - Guilford CT, US

Assignee:

President and Fellows of Harvard College - Cambridge MA

International Classification:

B41J 2/06

US Classification:

347055000

Abstract:

The present invention generally relates to systems and methods for the control of fluidic species and, in particular, to the coalescence of fluidic droplets. In certain instances, the systems and methods are microfluidic. In one aspect, the invention relates to systems and methods for causing two or more fluidic droplets within a channel to coalescence. The fluidic droplets may be of unequal size in certain cases. In some embodiments, a first fluidic droplet may be caused to move at a first velocity, and a second fluidic droplet may be caused to move at a second velocity different from the first velocity, for instance, substantially greater than the first velocity. The droplets may then coalesce, for example, upon application of an electric field. In the absence of an electric field, in some cases, the droplets may be unable to coalesce. In some cases, two series of fluidic droplets may coalesce, one or both series being substantially uniform. For instance, one series of droplets may have a distribution of diameters such that no more than about 5% of the droplets have a diameter greater than about 10% of the average diameter. In certain cases, one or more series of droplets may each consist essentially of a substantially uniform number of entities of a species therein (i.e., molecules, cells, particles, etc.). The fluidic droplets may be coalesced to start a reaction, and/or to stop a reaction, in some cases. For instance, a reaction may be initiated when a species in a first droplet contacts a species in a second droplet after the droplets coalesce, or a first droplet may contain an ongoing reaction and a second droplet may contain a species that inhibits the reaction. Other embodiments of the invention are directed to kits or methods for promoting the coalescence of fluidic droplets.

US Patent:

20080261295, Oct 23, 2008

Filed:

Jul 23, 2007

Appl. No.:

11/781848

Inventors:

William Frank Butler - La Jolla CA, US
Haichuan Zhang - San Diego CA, US
Philippe Marchand - Poway CA, US
Keunho Ahn - La Jolla CA, US
Yi Zhang - San Diego CA, US
John Francis - San Diego CA, US
Benjamin Lai - San Diego CA, US
Eugene Tu - San Diego CA, US

International Classification:

C12M 1/36
C12M 1/34
F16K 11/074

US Classification:

4352865, 4352871, 422 81, 436 53, 13762512, 137595

Abstract:

Apparatus and Methods are provided for a microfabricated fluorescence activated cell sorter based on a switch for rapid, active control of cell routing through a microfluidic channel network. This sorter enables low-stress, highly efficient sorting of populations of small numbers of cells (i.e., 1000-100,000 cells). The invention includes packaging of the microfluidic channel network in a self-contained plastic cartridge that enables microfluidic channel network to macro-scale instrument interconnect, in a sterile, disposable format. Optical and/or fluidic switching forces are used alone or in combination to effect switching.