The Charles Stark Draper Laboratory, Inc.

Axsun Technologies, Inc.

Microchips, Inc.

On Demand Therapeutics, Inc.

Massachusetts Institute of Technology

Microchips Biotech, Inc.

Jonathan Robert Coppeta

Jeffrey T Borenstein

Brett C Isenberg

John T Santini, Jr

Norman F Sheppard, Jr

Abigail June Spencer

Dale C Flanders

Scott Albert Uhland

Mark Joseph Mescher

Cynthia L Stevenson

Joseph L Charest

Robert J Dyer

Vishal Tandon

Douglas Snell

Norman F Sheppard

Kurt G Shelton

Peter S Whitney

Joseph D Cuiffi

Samuel Walker Inman

Robert K Jenner

Jenna Leigh Balestrini

Daniel F King

Zouhair Sbiaa

Transon Van Nguyen

Else M Vedula

Douglas B Snell

Catherine M Santini

Andrew I Poutiatine

John Anthony Scholl

Kenneth N Horne

Gregory M Fritz

Jeffrey A Korn

Benjamin F Polito

Robert Farra

Catherine M B Santini

Daniel Kenneth Freeman

Stephanie Lynne Golmon

Charles A Lissandrello

Jesse M Carr

Christina M Feakes

Kenneth L Hilts

Hesham Azizgolshani

Corin Williams

Steven C Fawcett

Brian Cain

Gregory J R Spooner

Naveed Shams

Douglas A Simpson

Timothy Petrie

Patricia A Swierk

Timothy J Biliouris

Gregory Spooner

John T Santini

Joseph Dennis Cuiffi

Robert Dyer

The methods and systems described herein provide a cell culture platform with an array of tissue modeling environments and dynamic control of fluid flow. The cell culture platform includes an array of wells that are fluidically coupled by microchannel structures. The dynamically controlled flow of fluid interacts with cells grown within the microchannels.

Bi-layer multi-well cell culture platform

A device, system and process involve conducting electroporation of microvesicles or exosomes or other target structures in a microfluidic arrangement at pressures that exceed atmospheric pressure. Single as well as multiple flow configurations can be employed. In some cases, the system and its operation are computer-controlled for partial or complete automation.

Method and device for high field strength electrotransfection of microvescicles and cells

Transfer of genetic and other materials to cells is conducted in a hands-free, automated, high throughput, continuous process. A system using a microfluidic hydrodynamic sheath flow configuration includes arrangements for pushing cells from side streams containing a cell culture medium to a central stream containing an electroporation buffer. Electroporation can be conducted in an assembly in which two or more microfluidic channels are provided in a parallel configuration and in which various layers can be stacked together to form a laminate type structure.

Method and apparatus for high throughput high efficiency transfection of cells

This disclosure provides systems and methods for seeding cell cultures in a microfluidic device. The systems and methods of this disclosure can enable flow of a cell solution from one side of a scaffold, such as a porous substrate or membrane, to the other side of the scaffold. Flow of the liquid can pass through the scaffold while the cells themselves do not, resulting in the cells driven to the surface of the scaffold for consequent attachment. A microfluidic device can include a microfluidic feature structured to create a seal between a cell seeding tool and an inlet to a microchannel of the microfluidic device. This can enable a pressure-driven flow to push fluid down the channel and through pores of the membrane. In contrast, traditional gravity fed seeding of cells may not create enough pressure to drive fluid through the pores of the scaffold.

Systems and methods for seeding cell cultures in a microfluidic device

According to various aspects and embodiments, a growth adaptive expandable stent is provided. The expandable stent includes a stent structure having a cylindrical shape that is self-expanding in a radial direction and includes a plurality of cylindrical rings disposed along a longitudinal axis of the stent structure. The stent structure is configured to exert a continuous outward radial force over time when implanted such that a diameter of the stent structure expands from a first value to a second value that is at least about 1.5 times the first value.

Growth adaptive expandable stent

A method and system of delivering a charged cargo, such as a biomolecule, to a target structure, such as cells, exosomes, other vesicles or micelles, using an electroactive porous membrane. This method comprises contacting an electroactive porous membrane with a fluid flow toward the membrane. The fluid contains charged biomolecules and the membrane and biomolecules are oppositely charged so that the biomolecules in the fluid are trapped on the membrane as the fluid flows through the pores of the membrane. Acceptor cells of interest are pinned to the membrane by the flow of the fluid, thereby aggregating the cells onto the membrane in close proximity to the trapped biomolecules. Finally, the acceptor cells are permeabilized.

Method and system for incorporation of biomolecules into vesicles, cells, and micelles using electroactive porous device membrane

Systems and methods disclosed herein related to an apparatus including a fluid flow plate and a microfluidic valve assembly. The fluid flow plate includes a plurality of polymer layers that define a fluid flow passage through the microfluidic valve assembly. The microfluidic valve assembly includes a valve seat, a flexible membrane, a valve cavity, a valve head, and an actuator. The actuator is configured to selectively control pressure applied by the valve head to the flexible membrane, such that in a first actuator state the valve head depresses the flexible membrane into the valve cavity and into contact with the valve seat, thereby preventing fluid flow through the valve assembly, and in a second state, the valve head and the flexible membrane are retracted substantially out of the valve cavity allowing fluid to flow through the valve assembly. In various implementations, the valve seat and/or the flexible membrane include an elastomer layer.

Actuated valve or pump for microfluidic devices

A destroy on-demand electrical device includes a substrate layer formed using a soluble material (e.g., a Germanium oxide), a semi-conductor layer formed from a material that can become soluble upon further processing (e.g., Germanium) and conductive elements, formed from a metallic material such as Copper. The device is coupled with one or more disintegration sources that contain disintegration agents (e.g., Hydrogen Peroxide) that can promote disintegration of the device. The device can be destroyed in response to actuation of the disintegration sources, for example by actuation of a source that produces Hydrogen Peroxide for use in oxidizing the semi-conductor layer. Water can be used to dissolve dissolvable substrate layers. The semi-conductor layer can be destroyed by first processing this layer to form a dissolvable material and dissolving the processed layer with water. The remaining Copper components disintegrate once their underlying layer have been dissolved and/or by use of a salt.

Method and apparatus for a destroy on-demand electrical device

Fluid circulation and leveling systems and methods of using the same are described. A fluid circulation system includes a fluid mixing chamber and open fluid chambers in fluid communication with the fluid mixing chamber. Each open fluid chamber includes a microfluidic fluid leveling conduit with an orifice disposed in the open fluid chamber at a minimum fluid level associated with a corresponding minimum fluid volume. A controller causes a first pump to generate a first direction of fluid flow during a first time period between the open fluid chambers, and causes the first pump to generate a second direction of fluid flow during a second time period between the first and second open fluid chambers. The controller also causes a second pump to generate a flow of fluid during a third time period from one of the first and second open fluid chambers into the fluid mixing chamber.

Fluid circulation systems incorporating fluid leveling devices

Compression cold welding methods, joint structures, and hermetically sealed containment devices are provided. The method includes providing a first substrate having at least one first joint structure which comprises a first joining surface, which surface comprises a first metal; providing a second substrate having at least one second joint structure which comprises a second joining surface, which surface comprises a second metal; and compressing together the at least one first joint structure and the at least one second joint structure to locally deform and shear the joining surfaces at one or more interfaces in an amount effective to form a metal-to-metal bond between the first metal and second metal of the joining surfaces. Overlaps at the joining surfaces are effective to displace surface contaminants and facilitate intimate contact between the joining surfaces without heat input. Hermetically sealed devices can contain drug formulations, biosensors, or MEMS devices.

Compression and cold weld sealing method for an electrical via connection

The systems and methods disclosed herein are generally related to a cell culture system. More particularly, the systems and methods enable the culturing and interconnecting of a plurality of tissue types in a biomimetic environment. By culturing organ specific tissue types within a biomimetic environment and interconnecting each of the organ systems in a physiologically meaningful way, experiments can be conducted on in vitro cells that substantially mimic the responses of in vivo cell populations. In some implementations, the organ systems are fluidically connected with a constant-volume pump.

Modular platform for multi-tissue integrated cell culture

An implantable drug delivery device that uses multiple reservoir elements to contain and release doses of active pharmaceutical ingredients. The device includes a first shell element, which has a first enclosed cavity volume and forms a low-permeability barrier. The first shell element is configured to absorb light irradiation from a laser source, the laser irradiation causing a breach in the first shell element. A first active pharmaceutical ingredient is contained in the first enclosed cavity volume and is released when the first shell element is breached. The device also includes a second shell element, which has a second enclosed cavity volume and also forms a low-permeability barrier. A second active pharmaceutical ingredient is contained in the second enclosed cavity volume. The device also includes an envelope element containing the first and second shell elements.

Low-permeability, laser-activated drug delivery device

Methods and systems are provided for making a drug microtablet. The method includes loading a lyophilization capillary channel with a liquid drug solution; lyophilizing the liquid drug solution in the lyophilization capillary channel to produce a lyophilized drug formulation; compressing the lyophilized drug formulation in the lyophilization capillary channel, or in a compression capillary channel, to form a microtablet; and ejecting the microtablet from the lyophilization capillary channel or compression capillary channel. The methods and systems may provide drug microtablets having improved content uniformity and reduced weight variability.

Microtablets for drug delivery

Growing community of inventors

Windham, NH, United States of America

Jonathan Robert Coppeta