Robert M Bonner

US Patent:

6420132, Jul 16, 2002

Filed:

Jan 31, 2000

Appl. No.:

09/495401

Inventors:

Robert F. Bonner - Washington DC
Seth R. Goldstein - Bethesda MD
Paul D. Smith - Annapolis MD
Thomas J. Pohida - Monrovia MD

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

G01N 130

US Classification:

435 405, 435 4052

Abstract:

Laser capture microdissection occurs where the transfer polymer film is placed on a substrate overlying visualized and selected cellular material from a sample for extraction. The transfer polymer film is focally activated (melted) with a pulse brief enough to allow the melted volume to be confined to that polymer directly irradiated. This invention uses brief pulses to reduce the thermal diffusion into surrounding non-irradiated polymer, preventing it from being heated hot enough to melt while providing sufficient heat by direct absorption in the small focal volume directly irradiated by the focused laser beam. This method can be used both in previously disclosed contact LCM, non contact LCM, using either condenser-side (or beam passes through polymer before tissue) or epi-irradiation (or laser passes through tissue before polymer). It can be used in configuration in which laser passes through tissue before polymer with and without an additional rigid substrate. In its preferred configuration it uses the inertial confinement of the surrounding unmelted thermoplastic polymer (and the overlying rigid substrate) to force expansion of the melted polymer into the underlying tissue target.

US Patent:

6569639, May 27, 2003

Filed:

Jan 18, 2001

Appl. No.:

09/765937

Inventors:

Lance A. Liotta - Potomac MD
Michael E. Buck - Bethesda MD
Rhonda Ann Weiss - Washington DC
Zhengping Zhuang - Bethesda MD
Robert F. Bonner - Washington DC

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

G01N 130

US Classification:

435 405, 100 4, 422 681

Abstract:

A method of microdissection which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes an activatable adhesive layer which provides chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated the transfer surface and tissue sample are separated. During separation the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample.

US Patent:

6720191, Apr 13, 2004

Filed:

Oct 30, 2000

Appl. No.:

09/601559

Inventors:

Seth R. Goldstein - Bethesda MD
Robert F. Bonner - Washington DC
Paul D. Smith - Annapolis MD
John Peterson - Falls Church VA
Thomas Pohida - Monrovia MD

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

G01N 100

US Classification:

436174, 436 43, 436 63, 435325, 422 50, 422 63, 422 64, 422 65, 422 66, 422 681

Abstract:

A method and apparatus of gathering by LCM identified cellular material from randorn locations on a tissue sample to designated locations on a transporting substrate enables convenient further processing. A transporting substrate has an identified mapped location for receiving identified cellular material. At least a segment of a selectively activatable coating is placed on the side of the transporting substrate in apposition to the tissue sample at the mapped location. The transporting substrate and sample are relatively moved to place the selectively activated coating at the mapped location in apposition to identified cellular material of the tissue sample which is to be extracted. Thereafter, the selectively activatable coating is activated and impressed or impressed and activated to form an adhesive region on the transporting substrate for adhering to the identified cellular material. Upon removal of the transporting substrate from the tissue sample, identified cellular material adheres to the transporting substrate at the mapped location.

US Patent:

6743601, Jun 1, 2004

Filed:

Dec 6, 1999

Appl. No.:

09/456042

Inventors:

Robert F. Bonner - Washington DC
Seth R Goldstein - Bethesda MD
Paul D. Smith - Annapolis MD
Thomas Pohida - Monrovia MD

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

G01N 130

US Classification:

435 405, 435 6, 435 721, 435 723, 435 4052, 436177, 382133, 428346, 428352

Abstract:

An apparatus and process for the micro juxtaposition is set forth where a selectively activatable surface is maintained spaced apart from the tissue sample and juxtaposed to the tissue sample by activation. In the typical case, activation occurs by laser radiation with the material of the activatable surface thermally expanding and bringing about the desired micro juxtaposition. The disclosed micro juxtapositioning can cause locally and microscopically pressure on tissue sample, insertion to the tissue sample, or contact of an activated or prepared surface to the tissue sample.

US Patent:

6783734, Aug 31, 2004

Filed:

Sep 1, 1999

Appl. No.:

09/387810

Inventors:

Seth R. Goldstein - Bethesda MD
Robert F. Bonner - Bethesda MD
Paul D. Smith - Bethesda MD
John Peterson - Bethesda MD
Thomas Pohida - Bethesda MD

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

B01L 1100

US Classification:

422101, 422 681, 422 99, 4352841, 4353071, 4353091, 436 63, 436174, 436175, 436177

Abstract:

A tissue sample is conventionally visualized in a microscope. A selectively activated convex surface is provided, preferably at the distal end of a rod. This selectively activated convex surface when activated, typically with a laser through an optic light path in the microscope, provides the activated region with adhesive properties. At least one portion of the tissue sample which is to be extracted is identified. This identified portion is contacted with a portion of the selectively activated convex surface on the end of the rod. When the convex surface is activated, typically by exposure to laser light in the footprint of the desired sample, an adhesive transfer surface on the selectively activated convex surface is provided which adheres to the desired cells in the footprint of the desired sample. Thereafter, the adhesive transfer surface is separated from the remainder of the tissue sample while maintaining adhesion with the desired cells. Thus the desired portion of the tissue sample is extracted.

US Patent:

6867038, Mar 15, 2005

Filed:

Feb 9, 2001

Appl. No.:

09/780234

Inventors:

Lance A. Liotta - Potomac MD, US
Michael Emmert-Buck - Silver Spring MD, US
David B. Krizman - Gaithersburg MD, US
Rodrigo Chuaqui - Las Condes, CL
W. Marston Linehan - North Bethesda MD, US
Jeffry M. Trent - Rockville MD, US
Robert F. Bonner - Washington DC, US
Seth R. Goldstein - Bethesda MD, US
Paul D. Smith - Annapolis MD, US
John I. Peterson - Falls Church VA, US

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

C12N005/00

US Classification:

435325, 435 29, 435 30, 435363, 435 11, 436 8

Abstract:

A method of microdissection which involves forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes a selectively activatable adhesive layer which provides, for example, chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated, the transfer surface and tissue sample are separated. During separation, the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample, the zone of cells of interest may then be molecularly analyzed.

US Patent:

6897038, May 24, 2005

Filed:

Apr 8, 2002

Appl. No.:

10/118487

Inventors:

Robert F. Bonner - Washington DC, US
Seth R. Goldstein - Bethesda MD, US
Paul D. Smith - Annapolis MD, US
Thomas J. Pohida - Monrovia MD, US

Assignee:

The United States of America as represented by the Secretary of the Department of Health and Human Services - Washington DC

International Classification:

G01N001/30

US Classification:

435 405, 435 4052

Abstract:

Laser capture microdissection occurs where the transfer polymer film is placed on a substrate overlying visualized and selected cellular material from a sample for extraction. The transfer polymer film is focally activated (melted) with a pulse brief enough to allow the melted volume to be confined to that polymer directly irradiated. This invention uses brief pulses to reduce the thermal diffusion into surrounding non-irradiated polymer, preventing it from being heated hot enough to melt while providing sufficient heat by direct absorption in the small focal volume directly irradiated by the focused laser beam. This method can be used both in previously disclosed contact LCM, non contact LCM, using either condenser-side (or beam passes through polymer before tissue) or epi-irradiation (or laser passes through tissue before polymer). It can be used in configuration in which laser passes through tissue before polymer with and without an additional rigid substrate. In its preferred configuration it uses the inertial confinement of the surrounding unmelted thermoplastic polymer (and the overlying rigid substrate) to force expansion of the melted polymer into the underlying tissue target.

US Patent:

7695752, Apr 13, 2010

Filed:

Aug 12, 2005

Appl. No.:

11/202848

Inventors:

Robert F. Bonner - Washington DC, US
Thomas J. Pohida - Monrovia MD, US
Michael R. Emmert-Buck - Easton MD, US
Michael Anthony Tangrea - Odenton MD, US
Rodrigo F. Chuaqui - North Potomac MD, US

Assignee:

The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services - Washington DC

International Classification:

B05D 1/00

US Classification:

427 213, 427 211, 427464, 4352831, 4352873, 356 36, 356 38, 356428, 428346

Abstract:

A device for performing target activated transfer that includes a mounting surface for mounting a tissue sample; and a light source positioned to substantially uniformly irradiate both stained and unstained regions of the tissue sample with light energy that activates the reagent to selectively adhere the stained regions to a transfer surface. Also described is an automated system for transferring tissue from a tissue sample to a transfer substrate. The system includes means for holding a tissue section that includes targets specifically stained with an absorptive stain thereby resulting in a stained tissue surface, and a flexible transfer film that includes a lower thermoplastic layer in sufficient thermal contact with the stained tissue surface; an irradiating assembly configured to provide a predetermined uniform light dose to the entire tissue section; and means for applying a constant pressure to the transfer film during irradiation.