公开(公告)号：US11203623B2

公开(公告)日：2021-12-21

申请号：US16892575

申请日：2020-06-04

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： Michael Super ,  Jeffrey Charles Way ,  Donald E. Ingber

IPC: C07K14/47 ,  C07K16/44 ,  C07K17/00 ,  G01N33/569 ,  G01N33/50 ,  G01N27/74

Abstract: The present invention provides for engineered molecular opsonins that may be used to bind biological pathogens or identify subclasses or specific pathogen species for use in devices and systems for treatment and diagnosis of patients with infectious diseases, blood-borne infections or sepsis. An aspect of the invention provides for mannose-binding lectin (MBL), which is an abundant natural serum protein that is part of the innate immune system. The ability of this protein lectin to bind to surface molecules on virtually all classes of biopathogens (viruses, bacteria, fungi, protozoans) make engineered forms of MBL extremely useful in diagnosing and treating infectious diseases and sepsis.

公开(公告)号：US11034744B2

公开(公告)日：2021-06-15

申请号：US16669805

申请日：2019-10-31

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： Alexander L. Watters ,  Donald E. Ingber ,  Mark J. Cartwright ,  Michael Super ,  Martin Rottman ,  Evangelia Murray ,  Brendon Dusel

IPC: C07K14/47 ,  G01N33/68 ,  G01N33/569 ,  A61K47/42 ,  A61K38/00

Abstract: Described herein are engineered microbe-targeting molecules, microbe-targeting articles, kits comprising the same, and uses thereof. Such microbe-targeting molecules, microbe-targeting articles, or the kits comprising the same can bind or capture of a microbe or microbial matter thereof, and can thus be used in various applications, such as diagnosis or treatment of an infection caused by microbes in a subject or any environmental surface.

公开(公告)号：US20210003561A1

公开(公告)日：2021-01-07

申请号：US17019102

申请日：2020-09-11

Applicant: President and Fellows of Harvard College

Inventor： Donald E. Ingber ,  Kambez Hajipouran Benam ,  Remi Villenave ,  Geraldine A. Hamilton ,  Bryan Hassell ,  Christopher D. Hinojosa ,  Carolina Lucchesi

IPC: G01N33/50 ,  C12M3/06 ,  C12M1/12 ,  C12M1/42 ,  C12M3/00 ,  C12M1/34

Abstract: Provided herein relates to systems and methods for producing and using a body having a central channel separated by one or more membranes. The membrane(s) are configured to divide the central channel into at least one mesochannel and at least one microchannel. The height of the mesochannel is substantially greater than the height of the microchannel. A gaseous fluid can be applied through the mesochannel while a liquid fluid flowing through the microchannel. The systems and methods described herein can be used for various applications, including, e.g., growth and differentiation of primary cells such as human lung cells, as well as any other cells requiring low shear and/also stratified structures, or simulation of a microenvironment in living tissues and/or organs (to model physiology or disease states, and/or to identify therapeutic agents and/or vaccines). The systems and methods can also permit co-culture with one or more different cell types.

公开(公告)号：US20200277558A1

公开(公告)日：2020-09-03

申请号：US16593646

申请日：2019-10-04

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： Donald E. Ingber ,  Daniel Levner ,  Guy Thompson, II ,  Jose Fernandez-Alcon ,  Christopher David Hinojosa

IPC: C12M1/00 ,  C12M3/06 ,  B01L3/00 ,  C12M3/00 ,  C12M1/12 ,  C12M1/36

Abstract: Systems and methods interconnect cell culture devices and/or fluidic devices by transferring discrete volumes of fluid between devices. A liquid-handling system collects a volume of fluid from at least one source device and deposits the fluid into at least one destination device. In some embodiments, a liquid-handling robot actuates the movement and operation of a fluid collection device in an automated manner to transfer the fluid between the at least one source device and the at least one destination device. In some cases, the at least one source device and the at least one destination device are cell culture devices. The at least one source device and the at least one destination device may be microfluidic or non-microfluidic devices. In some cases, the cell culture devices may be microfluidic cell culture devices. In further cases, the microfluidic cell culture devices may include organ-chips.

公开(公告)号：US20200270557A1

公开(公告)日：2020-08-27

申请号：US16648050

申请日：2018-09-18

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： Girija GOYAL ,  Bryan HASSELL ,  Donald E. Ingber

IPC: C12M3/06 ,  C12M3/00 ,  C12M1/12 ,  C12M1/42 ,  C12N5/09 ,  C12N5/071

Abstract: Disclosed herein are devices and methods for generating orthotopic models of cancer. The devices and methods include providing a microfluidic device having a body, the body including a first microchannel separated from a second microchannel by an at least partially porous membrane, the membrane having a first side facing the first microchannel and a second side facing the second microchannel, seeding the first side of the membrane with healthy cells and cancer cells such that the cancer cells are seeded with a differentiated tissue layer, and culturing the healthy cells and the cancer cells within the microfluidic device by flowing medium through one or more of the first and second microchannels with or without endothelium in the second channel.

公开(公告)号：US10732172B1

公开(公告)日：2020-08-04

申请号：US15576235

申请日：2016-05-22

Applicant: President and Fellows of Harvard College ,  Children's Medical Center Corporation

Inventor： Donald E. Ingber ,  Abhishek Jain ,  Andries D. van der Meer ,  Alan David Michelson ,  Andrew L. Frelinger, III ,  Riccardo Barrile

IPC: G01N33/50 ,  B01L3/00 ,  G01N33/86

Abstract: A method is directed to determining a thrombosis function and includes flowing a fluid sample over a surface having a fixed endothelial cell monolayer. The method further includes stimulating the fixed endothelial cell monolayer to induce formation of a clot, the clot being formed via interaction between the fixed endothelial cell monolayer and the fluid sample. In response to the clot formation, the method further includes determining a thrombosis function associated with the fluid sample and the fixed endothelial cell monolayer.

公开(公告)号：US20200095525A1

公开(公告)日：2020-03-26

申请号：US16496997

申请日：2018-03-26

Applicant: President and Fellows of Harvard College ,  The General Hospital Corporation

Inventor： David Benson Chou ,  Liliana S. Teixeira Moreira Leijten ,  Arianna Rech ,  Richard Novak ,  Donald E. Ingber ,  Yuka Milton ,  Viktoras Frismantas ,  Oren Levy

IPC: C12M3/06 ,  C12N5/077 ,  C12M1/00 ,  C12M1/12 ,  B01L3/00 ,  G01N33/50

Abstract: The present disclosure relates to a microfluidic devices and methods for culturing bone marrow cells. Aspects include methods of preparing microfluidic devices and culturing bone marrow cells with the microfluidic devices. In some aspects, a method includes providing a microfluidic device having an upper chamber, a lower chamber, and a porous membrane separating the upper chamber from the lower chamber. The method further includes seeding walls of the lower chamber and a bottom surface of the membrane with endothelial cells. The method further includes providing a matrix within the upper chamber. The matrix includes fibrin gel and bone marrow cells. The method further includes filling or perfusing the upper chamber with a media.

公开(公告)号：US20200055054A1

公开(公告)日：2020-02-20

申请号：US15781052

申请日：2016-12-02

Applicant: President and Fellows of Harvard College

Inventor： Kambez Hajipouran Benam ,  Donald E. Ingber ,  Richard Novak

IPC: B01L9/00 ,  C12M3/06 ,  C12M3/00 ,  C12M1/12

Abstract: A clamping system for a microfluidic device includes a compression plate engaging a side of a microfluidic device. A compression device provides compressive forces. The compression device is operatively connected to the compression plate such that the compressive forces create a substantially uniform pressure on the side of the microfluidic device.

公开(公告)号：US10526399B2

公开(公告)日：2020-01-07

申请号：US15415352

申请日：2017-01-25

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： Donald E. Ingber ,  Michael Super ,  Jeffrey Charles Way ,  Mark J. Cartwright ,  Julia B. Berthet ,  Dinah R. Super ,  Martin Rottman ,  Alexander L. Watters

IPC: C07K16/12 ,  G01N33/543 ,  G01N33/569 ,  C07K14/42 ,  A61K47/68

Abstract: Described herein are engineered microbe-targeting or microbe-binding molecules, kits comprising the same and uses thereof. Some particular embodiments of the microbe-targeting or microbe-binding molecules comprise a carbohydrate recognition domain of mannose-binding lectin, or a fragment thereof, linked to a portion of a Fc region. In some embodiments, the microbe-targeting molecules or microbe-binding molecules can be conjugated to a substrate, e.g., a magnetic microbead, forming a microbe-targeting substrate (e.g., a microbe-targeting magnetic microbead). Such microbe-targeting molecules and/or substrates and the kits comprising the same can bind and/or capture of a microbe and/or microbial matter thereof, and can thus be used in various applications, e.g., diagnosis and/or treatment of an infection caused by microbes such as sepsis in a subject or any environmental surface. Microbe-targeting molecules and/or substrates can be regenerated after use by washing with a low pH buffer or buffer in which calcium is insoluble.

公开(公告)号：US10513546B2

公开(公告)日：2019-12-24

申请号：US15105298

申请日：2014-12-18

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： Alexander L. Watters ,  Donald E. Ingber ,  Mark J. Cartwright ,  Michael Super ,  Martin Rottman ,  Evangelia Murray ,  Brendon Dusel

IPC: C07K14/47 ,  G01N33/569 ,  A61K47/42 ,  G01N33/68 ,  A61K38/00

Abstract: Described herein are engineered microbe-targeting molecules, microbe-targeting articles, kits comprising the same, and uses thereof. Such microbe-targeting molecules, microbe-targeting articles, or the kits comprising the same can bind or capture of a microbe or microbial matter thereof, and can thus be used in various applications, such as diagnosis or treatment of an infection caused by microbes in a subject or any environmental surface.