The Charles Stark Draper Laboratory, Inc.

Massachusetts Institute of Technology

Massachusetts Eye and Ear Infirmary

Vishal Tandon

Jeffrey T Borenstein

Jenna Leigh Balestrini

Jonathan Robert Coppeta

Marcello Peppi

Ernest Soonho Kim

Nathan Francis Moore

Kenneth T Kotz

Charles A Lissandrello

James Gillett Truslow

Bryan D Teece

Robert Samuel Langer

Marc Steven Weinberg

Jason Oliver Fiering

Joseph L Charest

Christopher M DiBiasio

Michael J McKenna

Daniel Kenneth Freeman

Louis Kratchman

William Sewell

Jose A Santos

Daniel F King

Ryan A Dubay

Rebecca Christianson

Erin Pararas

Peter Hsi

Andrew Ayoob

Patricia A Swierk

Dorit Berlin

Timothy J Biliouris

The present solution provides systems and methods for trans-round window membrane drug delivery. As an overview, a system can include a micropump that is connected to a flexible cannula. The cannula can be threaded through a handpiece that can be used to pierce the round window membrane of a patient. Using the handpiece, the cannula can be inserted through the round window membrane to improve the distribution of the delivered drug throughout the inner ear. The present solution can function as a small implantable or wearable device that can be used for both chronic and acute trans-round window membrane drug delivery. With this configuration, the micropump can constantly or intermittently deliver, over a period of days to months, small volumes of drugs from an internal reservoir.

Hand tool for aiding in insertion of a trans-round window membrane catheter for micropump-mediated acute and chronic inner-ear drug delivery

A device for treatment of cells with particles is disclosed. The device includes a semi-permeable membrane positioned between two plates, the first plate defining a first flow chamber and comprising a port, a flow channel, a transverse port, and a transverse flow channel, the first flow chamber constructed and arranged to deliver fluid in a transverse direction along the first side of the semi-permeable membrane, the second plate defining a second flow chamber and comprising a port. A method for transducing cells is disclosed. The method includes introducing a fluid with cells and viral particles into a flow chamber adjacent a semi-permeable membrane such that the cells and the viral particles are substantially evenly distributed on the semi-permeable membrane. The method also includes introducing a recovery fluid to suspend the cells and the viral particles, and separating the cells from the viral particles. A method of activating cells is disclosed.

Apparatus for efficient genetic modification of cells

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

The present solution provides trans-round window membrane (RWM) drug delivery. As an overview, the system can include a micropump that is connected to a flexible cannula. The cannula can include a stiffened and sharpened tip to facilitate insertion through the RWM. The cannula can be inserted through the RWM to improve the distribution of the delivered drug throughout the inner ear. The present solution can function as a small implantable or wearable device that can be used for both chronic and acute trans-RWM drug delivery. With this configuration, the micropump can constantly or intermittently deliver, over a period of days to months, small volumes of drugs from an internal reservoir.

Apparatus and method for trans-round window membrane drug delivery

Transfer of genetic and other materials to cells is conducted in a hands-free, automated and continuous process that includes flowing the cells between electroporation electrodes to facilitate delivery of a payload into the cells, while acoustophoretically focusing the cells. Also described is a control method for the acoustophoretic focusing of cells that includes detecting locations of cells flowing through a channel, such as with an image analytics system, and modulating a drive signal to an acoustic transducer to change the locations of the cells flowing in the channel. Finally, an electroporation driver module is described that uses a digital to analog converter for generating an electroporation waveform and an amplifier for amplifying the electroporation waveform for application to electroporation electrodes.

Method and apparatus for electroporation of acoustically-aligned cells

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

Microfluidic devices and associated methods are disclosed. A microfluidic device includes a target entrainment channel and an effluent channel on opposing sides of a semipermeable membrane. A restrictor channel that is narrower than the effluent channel is interposed between the semipermeable membrane and the effluent channel. Fluid that flows from the target entrainment channel, through the semipermeable membrane and the restrictor channel to the effluent channel, pins target cells along the center of the target entrainment channel for electroporation using an electrode in the channel.

Electroporation aided biological material delivery system and method

The present disclosure provides compositions and methods for treating an auditory disease in a subject in need thereof comprising administering an effective amount of a gel-based precursor that includes an inner ear-specific therapeutic compound directly into the cochlea of the subject.

Method and process for quantitative evaluation of pharmacokinetics, therapeutic effects and safety of delivery of drug compounds to the inner ear for treatment of auditory disease

Systems and methods are disclosed herein for use in transducing, activating, and otherwise treating cells. Cells are introduced into an inner layer of a multi-layered stack that defines at least one flow chamber and a plurality of cell entrainment regions. Vertical flow through the stack entrains the cells in the cell entrainment regions along with genetic information introduction agents or other additives, before the cells are washed using a reverse vertical flow and are collected from the device.

Systems and methods for cell transduction

Growing community of inventors

Roxbury Crossing, MA, United States of America

Vishal Tandon