Axion Biosystems, Inc.

Georgia Tech Research Corporation

University of Illinois

Biocircuit Technologies, Inc.

Swaminathan Rajaraman

James David Ross

Amanda Jervis Preyer

Isaac Perry Clements

Daniel Christopher Millard

Mark G Allen

Edgar A Brown

Bruce C Wheeler

Stephen P DeWeerth

Robert Dixon Grier, Jr

Robert Butera

Yong-Kyu Yoon

Yogi Anil Patel

Xiaosong Wu

Liang Guo

Yogi A Patel

Yanzhu Zhao

Gareth S Guvanasen

Phillip Edward Tyler

Ricardo Aguilar, Jr

Anthony Michael Nicolini

T Richard Nichols

Colin Michael Arrowood

Julian A Bragg

Robert J Butera

Seong-O Choi

Jung-Hwan Pauk

A neural interfacing device is disclosed. The neural interfacing device includes a microneedle electrode. The microneedle electrode includes a body having a void formed therein and a plurality of microneedles. The void surrounds the plurality of microneedles, and the plurality of microneedles are bent outward with respect to the body to form a three-dimensional microneedle electrode. Additionally, each of the plurality of microneedles is sized and shaped to penetrate a nerve epineurium.

Neural interfacing device

An electro-optical stimulation and recording system is disclosed, including a substrate and a plurality of wells coupled to the substrate. The system also includes at least one electrode set disposed proximate a respective one of the plurality of wells, wherein the electrode set comprises at least one electrode configured to collect an electric signal associated with at least a portion of the respective well. The system also includes a light-emitting element set corresponding to a respective one of the wells and configured to deliver optical stimulation to at least a portion of the respective well.

Multiwell microelectrode array with optical stimulation

A neural interfacing device is disclosed. The neural interfacing device may include at least one microneedle electrode. The microneedle electrode may have one or more microneedles. The one or more microneedles may be shaped and positioned such that when the neural interfacing device is applied to a nerve, the one or more microneedles penetrate a nerve epineurium without any portion of the microneedle electrode penetrating any nerve axon beyond a depth of 500 micrometers.

A cell-based biosensor array includes a base plate having a plurality of substantially transparent areas. The cell-based biosensor array also includes a flexible substrate coupled to the base plate and having disposed thereon a plurality of electrode sets, a plurality of terminal contacts, and a plurality of conductive traces. Each electrode set is disposed proximate a respective one of the substantially transparent areas, and each electrode set includes at least one electrode configured to detect an electric signal. Each terminal contact is associated with a respective one of the at least one electrode and disposed proximate a perimeter of the flexible substrate. Each conductive trace is electrically coupling a respective at least one electrode to the corresponding terminal contact. A first portion of flexible substrate including the electrode sets is disposed on a first surface of the base plate. A second portion of the flexible substrate including the terminal contacts is disposed on a second surface of the base plate.

Cell-based biosensor array and associated methods for manufacturing the same

Devices, systems, and methods for facilitating placement of cells and materials in culture plates configured for high-throughput applications are provided. A culture system is provided with a culture plate having a lid for guiding placement of cells and materials in each individual culture well of a culture plate. The lid may provide for coupling to an electrophysiology culture plate comprising a biosensor plate and a biologic culture plate, where the biosensor plate underlies and is coupled to the culture well plate such that each biosensor is operatively coupled to one culture well of the plurality of culture wells. A containment device that physically influences the positioning of fluid received in the culture plate is also provided herein.

Devices, systems, and methods for targeted plating of materials in high-throughput culture plates

Implementations disclosed herein provide for a microneedle electrode system comprising a microneedle electrode patch connected to external electronics. The microneedle electrode patch comprises a first flexible substrate having a plurality of conductive pads disposed thereon, a plurality of three-dimensional, individually addressable microneedle electrode arrays where each array has a plurality of microneedles extending from an upper surface thereof and a lower surface adapted to contact a corresponding one of the plurality of conductive pads disposed on the first substrate, and a second flexible substrate having a plurality of openings defined therein dimensioned to accommodate at least a portion of the upper surface of the microneedle electrode array from which the microneedles extend. Each of the conductive pads is disposed in electrical communication with a corresponding one of the plurality of microneedle electrode arrays and the first and second substrate are bonded together such that each one of the plurality of microneedle electrode arrays extends through a corresponding one of the plurality of openings defined in the second substrate.

Non-invasive segmentable three-dimensional microelectrode array patch for neurophysiological diagnostics and therapeutic stimulation

Electrophysiology culture plates are provided and are formed from a transparent microelectrode array (MEA) plate. The MEA plate comprises a substrate, a first layer and a first insulating layer. The substrate has a plurality of vias extending from an upper to a lower surface, each via being in electrical contact with each of a plurality of contact pads disposed on the lower surface. The first layer is disposed on the upper surface of the substrate and has a plurality of MEA arrays in electrical communication with at least a first routing layer. Each MEA array comprises a plurality of reference electrodes and a plurality of microelectrodes and the first routing layer is in electrical communication with a select number of the plurality of vias. A first insulating layer is disposed on the first layer. The MEA plate is joined to a biologic culture plate having a plurality of culture wells such that each culture well defines an interior cavity having a bottom surface that is at least partially transparent and in positioned in registration with a select optical port. The MEA plate is coupled to the biologic culture well plate such that each MEA array is operatively coupled to one culture well wherein each microelectrode and each reference electrode are in electrical communication with the interior cavity through the bottom surface of the culture well.

Devices, systems and methods for high-throughput electrophysiology

Methods are provided for fabricating three-dimensional electrically conductive structures. Three-dimensional electrically conductive microstructures are also provided. The method may include providing a mold having at least one microdepression which defines a three-dimensional structure; filling the microdepression of the mold with at least one substrate material; molding the at least one substrate material to form a substrate; and depositing and patterning of at least one electrically conductive layer either during the molding process or subsequent to the molding process to form an electrically conductive structure. In one embodiment, the three-dimensional electrically conductive microstructure comprises an electrically functional microneedle array comprising two or more microneedles, each including a high aspect ratio, polymeric three dimensional substrate structure which is at least substantially coated by an electrically conductive layer.

Method for making electrically conductive three-dimensional structures

Provided herein are apparatus and methods relating to the development of instrumentation for high throughput network electrophysiology and cellular analysis. More specifically, provided herein are multiwell microelectrode arrays (MEAs) and methods for the development of such an apparatus in an inexpensive fashion with a flexible, ANSI/SBS-compliant (American National Standards Institute/Society for Biomolecular Screening) format. Microelectrode arrays are a grid of tightly spaced microelectrodes useful for stimulating and sensing electrically active cells, networks and tissue. The techniques described herein relate to the use of microfabrication in combination with certain large-area processes that have been employed to achieve multiwell MEAs in ANSI/SBS-compliant culture well formats, which are also transparent for inverted/backside microscopy compatibility. These multiwell MEAs can be used to investigate two and three-dimensional networks of electrically active cells and tissue such as cardiac, neural, and muscular in a high throughput fashion. Also being ANSI/SBS-compliant, they are compatible with machinery and robotics developed for the pharmaceutical industry for drug screening applications.

Apparatus and methods for high throughput network electrophysiology and cellular analysis

Electrophysiology culture plates are provided and are formed from a transparent microelectrode array (MEA) plate. The MEA plate comprises a substrate, a first layer and a first insulating layer. The substrate has a plurality of vias extending from an upper to a lower surface, each via being in electrical contact with each of a plurality of contact pads disposed on the lower surface. The first layer is disposed on the upper surface of the substrate and has a plurality of MEA arrays in in electrical communication with at least a first routing layer. Each MEA array comprises a plurality of reference electrodes and a plurality of microelectrodes and the first routing layer is in electrical communication with a select number of the plurality of vias. A first insulating layer is disposed on the first layer. The MEA plate is joined to a biologic culture plate having a plurality of culture wells such that each culture well defines an interior cavity having a bottom surface that is at least partially transparent and in positioned in registration with a select optical port. The MEA plate is coupled to the biologic culture well plate such that each MEA array is operatively coupled to one culture well wherein each microelectrode and each reference electrode are in electrical communication with the interior cavity through the bottom surface of the culture well.

A 3D microelectrode device includes a flexible substrate containing poly-dimethyl siloxane (PDMS). The device may be fabricated in a miniature form factor suitable for attachment to a small organ such as a lateral gastrocnemius muscle of a live rat. In addition to providing a miniaturized, conformable attachment, the device provides an anchoring action via one or more microelectrodes, each having an insertable tip particularly shaped to provide the anchoring action. Furthermore, a base portion of each of the microelectrodes is embedded inside conductive poly-dimethyl siloxane (cPDMS). The cPDMS is contained in a pad that is coupled to a conductive track embedded in the flexible substrate. Embedding of the base portion inside the cPDMS material not only allows the microelectrode to bend in various directions, but also provides good electrical conductivity while eliminating the need for attachment processes using solder or epoxy adhesives.

Growing community of inventors

Atlanta, GA, United States of America

Swaminathan Rajaraman