Leland Stanford Junior University

United States of America As Represented by the Administrator of Nasa

Philip Huie, Jr

Daniel V Palanker

Alexander B Vankov

Harvey Abraham Fishman

Mark S Blumenkranz

Thomas W Chalberg, Jr

Robert M Waymouth

Michele P Calos

Stacey F Bent

Christopher N Ta

David J Loftus

Jaan Noolandi

Christina E Lee

Alan J Smith

Theodore Leng

Michael F Marmor

The present invention provides a method and apparatus for transferring an agent into a cell. The method includes the steps of providing an agent outside of a cell and generating a vapor bubble and a plasma discharge between an avalanche electrode and a conductive fluid surrounding the cell. The vapor bubble and plasma discharge generate a mechanical stress wave and an electric field, respectively. The combination of this mechanical stress wave and electric field results in permeabilization of the cell, which in turn results in transfer of the agent into the cell.

Method and apparatus for avalanche-mediated transfer of agents into cells

The present invention provides a method of treating an ocular disease in a subject. In a first step, a nucleic acid is introduced into cells or a tissue. The nucleic acid is introduced by electron avalanche transfection. With this technique, a high electric field induces a vapor bubble and plasma discharge between an electrode and the surrounding medium. The formation of a vapor bubble generates mechanical stress. Plasma discharge through the ionized vapor in the bubble enables connectivity between the electrode and the surrounding medium, so that mechanical stress and electric field are applied simultaneously, which results in permeabilization of the cells or tissue. This permeabilization in turn allows the nucleic acid to enter the cell or tissue. Cells or tissue containing the nucleic acid are then transplanted into an ocular region of the subject.

Ocular gene therapy using avalanche-mediated transfection

A nanotube mat is provided with an array of conduits to support, direct growth, select or interface one or more biological cells or cell processes. The carbon nanotube mat provides mechanical stability, is biocompatible, will support cell growth, can desirably be derivatized with growth factors, molecules, nutrients, inhibitory factors, ligands, transduction molecules or morphogenic factors, and would allow the formation of conduits to guide cells and cell extensions to be hosted or grown. The conduits could take any size or shape to support, direct growth, select or interface one or more cells or processes. In general the conduits could be channels, discontinuous channels, tapered channels or walls. The nanotube mat could be used to interface biological cells with other cells, tissue or structures that have electrical, mechanical, magnetic means, or optical means. The nanotube mat could also incorporate chemicals, analytes, drugs, lips, carbohydrates, secretory products or the like.

Nanotube mat with an array of conduits for biological cells

A method for repairing a retinal system of an eye, using bucky paper on which a plurality of retina pigment epithelial cells and/or iris pigment epithelial cells and/or stem cells is deposited, either randomly or in a selected cell pattern. The cell-covered bucky paper is positioned in a sub-retinal space to transfer cells to this space and thereby restore the retina to its normal functioning, where retinal damage or degeneration, such as macular degeneration, has occurred.

Bucky paper as a support membrane in retinal cell transplantation

An interface for selective excitation or sensing of neural cells in a biological neural network is provided. The interface includes a membrane with a number of channels passing through the membrane. Each channel has at least one electrode within it. Neural cells in the biological neural network grow or migrate into the channels, thereby coming into close proximity to the electrodes. Once one or more neural cells have grown or migrated into a channel, a voltage applied to the electrode within the channel selectively excites the neural cell (or cells) in that channel. The excitation of these neural cell(s) will then transmit throughout the neural network (i.e. cells and axons) that is associated with the neural cell(s) stimulated in the channel.

Interface for making spatially resolved electrical contact to neural cells in a biological neural network

The invention provides implants suitable for use as an artificial cornea, and methods for making and using such implants. Artificial corneas having features of the invention may be two-phase artificial corneas, or may be three phase artificial corneas. These artificial corneas have a flexible, optically clear central core and a hydrophilic, porous skirt, both of which are biocompatible and allow for tissue integration. A three-phase artificial cornea will further have an interface region between the core and skirt. The artificial corneas have a high degree of ocular tolerance, and allow for tissue integration into the skirt and for epithelial cell growth over the surface of the prosthesis. The use of biocompatible material avoids the risk of disease transmission inherent with corneal transplants, and acts to minimize post-operative inflammation and so to reduce the chance or severity of tissue necrosis following implantation of the synthetic cornea onto a host eye.

Artificial cornea

Methods and apparatus for modifying membranous tissue, growing cells on modified membranous tissue, and for transplantation of modified tissues and modified tissues with attached cells are provided. In particular, the invention provides methods and apparatus for modifying membranous tissue such as lens capsule tissue and inner limiting membrane tissue, for growing cells such as iris pigment epithelial (IPE) cells and retinal pigment epithelial (RPE) cells on modified membranous tissue, and for modifying membranous tissue and growing cells on biodegradable polymer substrates. A method of modifying membranous tissues comprises depositing micropatterns of biomolecules onto membranous tissue with a contacting surface such as a stamp; other methods include mechanical ablation, photoablation, ion beam ablation, and modification of membranous tissues via the action of proteolytic enzymes.

Growing community of inventors

Cupertino, CA, United States of America

Philip Huie, Jr