公开(公告)号：US20240210320A1

公开(公告)日：2024-06-27

申请号：US17427540

申请日：2020-01-31

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Michael Levene ,  Richard Torres

IPC: G01N21/64 ,  G01N33/53 ,  G02B21/00 ,  G02B21/26

CPC classification number: G01N21/6458 ,  G01N21/6428 ,  G01N33/5308 ,  G02B21/0076 ,  G02B21/0084 ,  G02B21/26 ,  G01N2021/6439 ,  G01N2021/6463 ,  G01N2201/06113 ,  G01N2201/105

Abstract: The invention provides improved systems and methods for multiphoton microscopy including pixel clocking techniques for minimizing pixel integration time and providing consistent signal intensity with maximized imaging speeds. Various systems and method are described for optimizing laser repetition rate based on dye lifetime, combining polygonal mirror scanning and stage translation, using the laser pulse signal to time pixel collection, and minimizing laser pulses and dye usage based on signal to background ratios.

公开(公告)号：US20230204474A1

公开(公告)日：2023-06-29

申请号：US18154447

申请日：2023-01-13

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Michael Levene ,  Richard Torres

IPC: G01N1/36 ,  G01N1/30 ,  G06T7/00 ,  C12M1/12

CPC classification number: G01N1/36 ,  G01N1/30 ,  G06T7/0012 ,  C12M25/06 ,  C12M23/04 ,  G01N2001/302 ,  G01N2001/305

Abstract: The present invention relates to systems and methods for tissue processing and analysis. Tissue chambers are configured to allow single-container chemical processing, imaging, and wax embedding of tissue samples in a single container without manipulation between steps. Tissue chambers with features to support the tissue sample and allow fluid flow between the tissue sample and the tissue chamber surface are disclosed. The features may be index matched to sample structures of interest or dissolvable in clearing solution to allow for in-chamber imaging with minimal distortion. Specialized tissue processing and wax removal apparatuses are also disclosed including for use with tissue chambers having frangible portions to permit ease of wax removal.

公开(公告)号：US20190360901A1

公开(公告)日：2019-11-28

申请号：US16164343

申请日：2018-10-18

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Michael Levene ,  Richard Torres

IPC: G01N1/36 ,  G01N1/30 ,  G06T7/00 ,  C12M1/12

Abstract: The present invention relates to systems and methods for tissue processing and analysis. Tissue chambers are configured to allow single-container chemical processing, imaging, and wax embedding of tissue samples in a single container without manipulation between steps. Tissue chambers with features to support the tissue sample and allow fluid flow between the tissue sample and the tissue chamber surface are disclosed. The features may be index matched to sample structures of interest or dissolvable in clearing solution to allow for in-chamber imaging with minimal distortion. Specialized tissue processing and wax removal apparatuses are also disclosed including for use with tissue chambers having frangible portions to permit ease of wax removal.

公开(公告)号：US11573179B2

公开(公告)日：2023-02-07

申请号：US17000994

申请日：2020-08-24

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Richard Torres ,  Michael Levene

IPC: G01N1/30 ,  G01N21/64 ,  G01N33/483

Abstract: The present invention relates to systems and methods for tissue processing and imaging including a counterintuitive inverse relationship between protein dye concentration and tissue sample protein content. Varying dye concentration in such a manner affords higher quality fluorescent imaging at depth in tissue when using optical sectioning microscopy or second harmonic generation (SHG) analysis. Methods of the invention thereby provide more usable histopathology images while reducing waste and reagent costs and are of particular utility in combination assays that include simultaneous protein and nuclear staining and SHG analysis.

公开(公告)号：US11555765B2

公开(公告)日：2023-01-17

申请号：US16735061

申请日：2020-01-06

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Michael Levene ,  Richard Torres

IPC: G01N1/00 ,  G01N1/36 ,  G01N1/30 ,  G06T7/00 ,  C12M1/12

Abstract: The present invention relates to systems and methods for tissue processing and analysis. Tissue chambers are configured to allow single-container chemical processing, imaging, and wax embedding of tissue samples in a single container without manipulation between steps. Tissue chambers with features to support the tissue sample and allow fluid flow between the tissue sample and the tissue chamber surface are disclosed. The features may be index matched to sample structures of interest or dissolvable in clearing solution to allow for in-chamber imaging with minimal distortion. Specialized tissue processing and wax removal apparatuses are also disclosed including for use with tissue chambers having frangible portions to permit ease of wax removal.

公开(公告)号：US20210072156A1

公开(公告)日：2021-03-11

申请号：US17000994

申请日：2020-08-24

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Richard Torres ,  Michael Levene

IPC: G01N21/64 ,  G01N33/483

Abstract: The present invention relates to systems and methods for tissue processing and imaging including a counterintuitive inverse relationship between protein dye concentration and tissue sample protein content. Varying dye concentration in such a manner affords higher quality fluorescent imaging at depth in tissue when using optical sectioning microscopy or second harmonic generation (SHG) analysis. Methods of the invention thereby provide more usable histopathology images while reducing waste and reagent costs and are of particular utility in combination assays that include simultaneous protein and nuclear staining and SHG analysis.

公开(公告)号：US20200371033A1

公开(公告)日：2020-11-26

申请号：US16895498

申请日：2020-06-08

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Michael Levene ,  Richard Torres

IPC: G01N21/64

Abstract: The invention provides improved systems and methods for multiphoton microscopy including pixel clocking techniques for minimizing pixel integration time and providing consistent signal intensity with maximized imaging speeds. Various systems and method are described for optimizing laser repetition rate based on dye lifetime, combining polygonal mirror scanning and stage translation, using the laser pulse signal to time pixel collection, and minimizing laser pulses and dye usage based on signal to background ratios.

公开(公告)号：US20200348216A1

公开(公告)日：2020-11-05

申请号：US16735061

申请日：2020-01-06

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Michael Levene ,  Richard Torres

IPC: G01N1/36 ,  G01N1/30 ,  G06T7/00 ,  C12M1/12

Abstract: The present invention relates to systems and methods for tissue processing and analysis. Tissue chambers are configured to allow single-container chemical processing, imaging, and wax embedding of tissue samples in a single container without manipulation between steps. Tissue chambers with features to support the tissue sample and allow fluid flow between the tissue sample and the tissue chamber surface are disclosed. The features may be index matched to sample structures of interest or dissolvable in clearing solution to allow for in-chamber imaging with minimal distortion. Specialized tissue processing and wax removal apparatuses are also disclosed including for use with tissue chambers having frangible portions to permit ease of wax removal.

公开(公告)号：US10677730B1

公开(公告)日：2020-06-09

申请号：US16523698

申请日：2019-07-26

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Michael Levene ,  Richard Torres

IPC: G01N21/64

Abstract: The invention provides improved systems and methods for multiphoton microscopy including pixel clocking techniques for minimizing pixel integration time and providing consistent signal intensity with maximized imaging speeds. Various systems and method are described for optimizing laser repetition rate based on dye lifetime, combining polygonal mirror scanning and stage translation, using the laser pulse signal to time pixel collection, and minimizing laser pulses and dye usage based on signal to background ratios.

公开(公告)号：US10591392B2

公开(公告)日：2020-03-17

申请号：US14324019

申请日：2014-07-03

Applicant: APPLIKATE TECHNOLOGIES LLC

Inventor： Richard Torres ,  Michael Levene

IPC: G01N1/30 ,  G01N33/483

Abstract: A biopsy-sized tissue sample is stained for quick imaging. A significant amount of permeation enhancer is included in a mixed solution of permeant enhancer, fixative or dehydrant, and one or two fluorescent dyes to simultaneously dehydrate and dye the tissue sample. The permeation enhancer, e.g., 10% to 50% in the mixed solution, achieves an image of dyed tissue in the contacted tissue sample at a depth of at least 200 um within no more than 1.5 hours. One of the fluorescent dyes is a fluorescent nuclear dye such as DAPI, SYTOX green, acridine orange, propidium iodide, or a Hoechst dye. The other fluorescent dye is a fluorescent protein dye such as eosin or rhodamine B. The tissue sample is cleared with a clearing agent having a refractive index of at least 1.4[R2], e.g., using BABB. The mixed solution may further include Chloroform or other morphology preservative.