Abstract: A scalable, real-time, label-free, electrode- or optical-based cell monitoring system for integration into a cell culture incubator is described herein. An example system includes (1) cell culture consumables with integrated electrodes and/or optics for growing and monitoring cells, (2) incubator trays for consumable organization and recording, and (3) a system console, external to the incubator, for connecting multiple incubator trays. Without perturbing the cell culture, the system is capable of monitoring multiple culture attributes for each cell culture consumable simultaneously. These attributes can include, but are not limited to, cell growth, proliferation, morphology, media pH, or media oxygen. The system can support multiple trays, which permits monitoring dozens to hundreds of consumables simultaneously, including a mixture of consumables of various sizes. In addition to monitoring adherent cells, the disclosed technology can be readily adapted for monitoring of cell suspensions.

Abstract: 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.

Abstract: Disclosed herein are systems and methods for assessing electrically active cell cultures. Optionally, the data can be collected using a microelectrode array (MEA). For example, electrically active cells, such as cardiomyocytes, are cultured such that they are in electrical communication with at least a portion of the electrodes of a well of the MEA. The assessments derived from the disclosed methods may be used to reduce the effects of confounding variables in data obtained from an electrically active cell culture. The methods may also be used to determine a quantitative measure of arrhythmia burden. The methods may also be used to decide if a particular culture or set of data is suitable for inclusion in scientific and characterization studies. Also disclosed is a method of finding the global conduction velocity of an electrically active cell culture.

Abstract: Systems and methods for creating a localized environment for a cell culture plate are described herein. An example system can include a dock shaped to receive the cell culture plate, and a gas distribution device positioned on the dock. The gas distribution device can include a frame including a plurality of sides connected to form an opening, an internal channel within the frame for directing a gas mixture within the gas distribution device, an inlet port in fluid communication with the internal channel for receiving the gas mixture, and a plurality of apertures in fluid communication with the internal channel. The plurality of apertures can be spaced apart from one another along the frame and configured to direct the gas mixture toward the opening.

Abstract: 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.

Abstract: 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.

Abstract: Disclosed herein are systems and methods for assessing electrically active cell cultures. Optionally, the data can be collected using a microelectrode array (MEA). For example, electrically active cells, such as cardiomyocytes, are cultured such that they are in electrical communication with at least a portion of the electrodes of a well of the MEA. The assessments derived from the disclosed methods may be used to reduce the effects of confounding variables in data obtained from an electrically active cell culture. The methods may also be used to determine a quantitative measure of arrhythmia burden. The methods may also be used to decide if a particular culture or set of data is suitable for inclusion in scientific and characterization studies. Also disclosed is a method of finding the global conduction velocity of an electrically active cell culture.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.