Robert J 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:

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:

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.

US Patent:

8460744, Jun 11, 2013

Filed:

Feb 25, 2010

Appl. No.:

12/713105

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 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, 4352871, 356 36, 356 38, 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.

US Patent:

20040053326, Mar 18, 2004

Filed:

Jul 10, 2003

Appl. No.:

10/333374

Inventors:

Michael Emmert-Buck - Silver Spring MD, US
Chad Haldeman-Englert - Mesa AZ, US
Robert Bonner - Washington DC, US
Lance Liotta - Bethesda MD, US

International Classification:

G01N033/53

US Classification:

435/007100

Abstract:

The present disclosure concerns methods, systems, and devices for analyzing a biological material, such as a cellular or other specimen. In one disclosed example, the method selectively transfers biomolecules from a target region of interest in a biological sample (such as a tissue section). The transfer may occur, for example, by selectively focally altering a characteristic of a transfer layer adjacent the target region, such that the biomolecules can move through the altered area of the transfer layer. In particular examples, the transfer layer is altered by focally increasing a permeability of the transfer layer, for example by removing a focal portion of the transfer layer, and transporting the biomolecules through the altered region of the transfer layer, to microdissect the biomolecules of interest from the biological sample. In yet other embodiments, the microdissected biomolecules can be applied to an analysis substrate containing an identification molecule, such as a nucleic acid array, layered expression scan, or wells containing antibodies. Transfer microdissection allows biomolecules from regions of interest in the biological specimen to be selectively analyzed. For example, nests of highly a typical or metastatic cells in a tumor section can be analyzed for differential expression of certain proteins.

US Patent:

45224943, Jun 11, 1985

Filed:

Jul 7, 1982

Appl. No.:

6/396057

Inventors:

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 3348
G01N 2153

US Classification:

356 39

Abstract:

A system for assessing platelet viability in a transparent flexible bag. The apparatus employed consists of a support for clampingly receiving the bag and defining an optically exposed constricted region in the bag. A laser beam is passed perpendicularly through the constricted region of the bag. The opposite side portions of the bag are alternately periodically compressed and released to provide laminar fluid flow through the constricted region to align platelet discs face-on with respect to the beam. Scattered light from the beam is passed through an annular gate, defining a selected scatter angle relative to the beam axis. The selected scattered light is directed by a lens onto a photodiode detector. The output of the detector is processed and furnished to a computer, which is employed to derive respective quantities indicating the concentration of non-aggregated platelets and the percentage that are discs. These quantities are obtainable by (1) averaging the output during a period when said laminar flow is provided, to obtain a value I. sub.