Heather T Clark

US Patent:

7910065, Mar 22, 2011

Filed:

Oct 16, 2009

Appl. No.:

12/580749

Inventors:

Heather Clark - Lexington MA, US

Assignee:

The Charles Stark Draper Laboratory, Inc. - Cambridge MA

International Classification:

G01N 21/01

US Classification:

422 8206, 435 71

Abstract:

Chemical reactions occurring within a living cell are measured in a manner that does not affect the viability of the cell or the reaction under study. In one embodiment, one or more sensors are introduced into the cell and/or covalently associated with the exterior cell membrane. The sensor(s) emit an observable signal indicating a value of a parameter associated with the chemical reaction, e. g. , the concentration of a reaction product. Because cell viability is not compromised, the cell may be stimulated (e. g. , by subjection to an agonist or antagonist, a pathogen, a pharmaceutical compound, or a potential toxin) so as to affect the reaction under study.

US Patent:

8114662, Feb 14, 2012

Filed:

Jul 31, 2007

Appl. No.:

11/888663

Inventors:

Heather A. Clark - Lexington MA, US
Daniel I. Harjes - Cambridge MA, US
John M. Dubach - Somerville MA, US

Assignee:

The Charles Stark Draper Laboratory, Inc. - Cambridge MA

International Classification:

G01N 33/53
C12M 1/34
B82B 3/00
C12Q 1/02
C12Q 1/20

US Classification:

4352887, 435 71, 435 29, 977774

Abstract:

The invention provides ion-selective sensors comprising quantum dots capable of selectively measuring ions, e. g. , Na, K, Cl, etc. , in various environments, including in the cytosol of a living cell. Quantum dots are attractive probes for microscopy due to their photophysical advantages over fluorescent dyes, including prolonged photostability, brightness and quantum efficiency. In certain embodiments, a sensor comprises one or more quantum dots, a pH-sensitive dye, and optionally an ion-selective component such as an ionophore. These elements may, for example, be disposed in a polymer matrix. In certain embodiments, the sensors may detect ionic analytes by selective ion extraction by the polymer, thereby inducing a pH change within the sensor which in turn changes the absorbance of the pH-sensitive dye. The change of absorbance may in turn attenuate the intensity of detectable emissions, e. g. , fluorescence, from the quantum dot by directly absorbing its fluorescence emission.

US Patent:

8263358, Sep 11, 2012

Filed:

Oct 14, 2008

Appl. No.:

12/287937

Inventors:

Heather A. Clark - Lexington MA, US
Daniel I. Harjes - Allston MA, US
John M. Dubach - Somerville MA, US

Assignee:

The Charles Stark Draper Laboratory, Inc. - Cambridge MA

International Classification:

C12Q 1/02
C12M 1/00
G01N 33/53
G01N 33/52
A61K 49/00
B82B 3/00

US Classification:

435 29, 424 96, 435 71, 4352887, 977774, 977927

Abstract:

The invention provides ion-selective sensors capable of selectively measuring ions, e. g. , Na, K, Cl, etc. , in the cytosol of a single living cell. The sensor comprises one or more quantum dots or a fluorescent dye, a pH-sensitive dye, and optionally an ion-selective component such as an ionophore. These elements may, for example, be disposed in a polymer matrix. The polymer matrix comprises an internalizing moiety which enables the sensor to localize within the cytosol of a cell. The internalizing moiety comprises a small molecule or peptide such as an amine, antepennepedia, mastoparan, or melittin that react under acidic conditions to release a sensor from the confines of a endosome. Once in the cytosol the sensors may detect ionic analytes by selective ion extraction by the polymer, thereby inducing a pH change within the sensor which in turn changes the absorbance of the pH-sensitive dye. The change of absorbance may in turn attenuate the intensity of detectable emissions, e. g. , fluorescence, from the quantum dot or dye by directly absorbing its fluorescence emission.

US Patent:

8268567, Sep 18, 2012

Filed:

Sep 15, 2006

Appl. No.:

11/522169

Inventors:

Heather Clark - Lexington MA, US

Assignee:

The Charles Stark Draper Laboratory - Cambridge MA

International Classification:

G01N 33/53

US Classification:

435 71, 435 4

Abstract:

Chemical reactions occurring within a living cell are measured in a manner that does not affect the viability of the cell or the reaction under study. In one embodiment, one or more sensors are introduced into the cell and/or covalently associated with the exterior cell membrane. The sensor(s) emit an observable signal indicating a value of a parameter associated with the chemical reaction, e. g. , the concentration of a reaction product. Because cell viability is not compromised, the cell may be stimulated (e. g. , by subjection to an agonist or antagonist, a pathogen, a pharmaceutical compound, or a potential toxin) so as to affect the reaction under study.

US Patent:

8470300, Jun 25, 2013

Filed:

Sep 8, 2009

Appl. No.:

12/584528

Inventors:

Heather A. Clark - Lexington MA, US
Karen K. Gleason - Cambridge MA, US
Salmaan Baxamusa - Cambridge MA, US
John M. Dubach - Somerville MA, US

Assignee:

The Charles Stark Draper Laboratory, Inc. - Cambridge MA
Massachusetts Institute of Technology - Cambridge MA

International Classification:

A61K 49/00
C12Q 1/02

US Classification:

424 96, 424417, 424489

Abstract:

The invention provides coated sensors for detecting the presence of analytes. The sensor comprises one or more fluorescent sources, such as one or more quantum dots or one or more fluorescent dyes, a polymeric matrix, a surface coating, and one or more analyte sensing components. The surface coating may be a conformal polymeric film, permeable to the analyte, which may be deposited via a solventless process such as initiated chemical vapor deposition or photoinitiated chemical vapor deposition. The surface coating may increase the biocompatibility of the sensor, reduce nonspecific protein adsorption, and/or sequester functional sensor components within the sensor. The invention also provides methods for detecting the presence of an analyte with coated sensors of the invention.

US Patent:

20080044879, Feb 21, 2008

Filed:

Aug 22, 2006

Appl. No.:

11/507956

Inventors:

Daniel I. Harjes - Cambridge MA, US
Heather A. Clark - Lexington MA, US

Assignee:

The Charles Stark Draper Laboratory, Inc. - Cambridge MA

International Classification:

C12N 13/00

US Classification:

4351736

Abstract:

Systems and methods are provided for optically measuring ion concentrations in biological samples. The systems and methods employ polymer-based optical ion sensors that include ion-selective ionophores and a pH sensitive chromionophore. Electrodes are providing for electrically stimulating the biological samples.

US Patent:

20090155183, Jun 18, 2009

Filed:

Jun 6, 2008

Appl. No.:

12/156959

Inventors:

Heather A. Clark - Lexington MA, US

Assignee:

The Charles Stark Draper Laboratory, Inc. - Cambridge MA

International Classification:

A61K 49/00
G01N 21/00
C12Q 1/02
C12Q 1/54

US Classification:

424 96, 436164, 435 29, 435 14, 977774

Abstract:

The systems and methods disclosed herein include a sensor particle for detecting the presence of a chelatable analyte, such as glucose, wherein the sensor comprises a chromophore and a fluorescent component, such as a quantum dot. The sensor particle further comprises moieties that bind both a clelatable analyte and chromophore reversibly and competitively. In the presence of the chelatable analyte, the moieties bind the analyte, and release the chromophore. The chromophore absorbs photons of one wavelength in a free state but of a different wavelength in a bound state, and is selected to operate with the fluorescent component such that the chromophore absorbs emissions of the fluorescent substance in only one of the bound and unbound states. In certain aspects, the invention comprises methods for detecting the presence of a chelatable analyte in a medium such as water, blood plasma and urine, using the sensor particles of the invention.

US Patent:

20100105075, Apr 29, 2010

Filed:

Oct 15, 2009

Appl. No.:

12/579983

Inventors:

Daniel I. Harjes - Cambridge MA, US
Heather A. Clark - Lexington MA, US

Assignee:

The Charles Stark Draper Laboratory, Inc. - Cambridge MA

International Classification:

C12Q 1/02

US Classification:

435 72

Abstract:

Systems and methods are provided for optically measuring ion concentrations in biological samples. The systems and methods employ polymer-based optical ion sensors that include ion-selective ionophores and a pH sensitive chromionophore. Electrodes are providing for electrically stimulating the biological samples.