Device and method for preparing compartmentalized in vitro models with neuronal cells

A cell culture device for preparing a compartmentalized in vitro model using neuronal cells, the cell culture device comprising:

• a multi-well insert insertable in a reservoir of a cell culture plate, the reservoir being configured to receive a culture medium fluid therein, the multi-well insert comprising:
• a plurality of insert wells each comprising a bottom wall having a microfluidic layer-receiving portion on a top surface thereof;
• a microfluidic layer receivable on the microfluidic layer-receiving portion of a corresponding one of the plurality of insert wells, the microfluidic layer comprising channels for orienting axonal growth;
• and
• an upwardly extending feed well provided in proximity of a corresponding one of the plurality of insert wells, the upwardly extending feed well comprising a seeding chamber extending longitudinally therethrough and being configured to receive the neuronal cells therein, the seeding chamber being configured to be in fluid communication with the channels of the microfluidic layer.

A cell culture device for preparing a compartmentalized in vitro model using neuronal cells, the cell culture device comprising:

• a cell culture plate defining a reservoir having a microfluidic layer-receiving portion on a top surface thereof;
• a microfluidic layer receivable on the microfluidic layer-receiving portion of the reservoir of the cell culture plate, the microfluidic layer comprising channels for orienting axonal growth;
• a multi-well insert insertable in the reservoir of a cell culture plate onto the microfluidic layer, the multi-well insert comprising a plurality of insert wells that are bottomless;
• and
• an upwardly extending feed well provided in proximity of a corresponding one of the plurality of insert wells, the upwardly extending feed well comprising a seeding chamber extending longitudinally therethrough and being configured to receive the neuronal cells therein, the seeding chamber being configured to be in fluid communication with the channels of the microfluidic layer.

A cell culture device for use with a microfluidic layer for preparing a compartmentalized in vitro model, the cell culture device comprising:

• an insert insertable in a reservoir of a cell culture plate, the reservoir being configured to receive a culture medium fluid therein, the insert comprising:
• a bottom wall having a microfluidic layer-receiving portion on a top surface thereof;
• and
• an upwardly extending feed well comprising a seeding chamber extending longitudinally therethrough and being configured to receive neuronal cells therein, the seeding chamber being configured to be in fluid communication with channels of a microfluidic layer.

A method for preparing a compartmentalized in vitro model within a reservoir of a cell culture plate, the method comprising:

• placing a cover on a top surface of a microfluidic layer that is received into the reservoir, the microfluidic layer comprising channels configurable in an open-top configuration and in a close-top configuration, to cover the channels and provide the close-top configuration;
• seeding neuronal cells in a seeding chamber of a feed well provided in proximity of the microfluidic layer, the seeding chamber being in fluid communication with the channels of the microfluidic layer;
• supplying a cell culture medium to the seeding chamber and to the channels;
• after a time period during which axons of the neuronal cells have grown within the channels and have reached a given length within the channels, removing the cover to uncover the channels and provide the open-top configuration;
• placing a biological model onto the top surface of the microfluidic layer;
• and
• filing the reservoir with the cell culture medium up to a given level, wherein a proximity of the neuronal cells and the biological model enables interaction therebetween.

A method for preparing a compartmentalized in vitro model within a reservoir of a cell culture plate, the method comprising:

• placing a biological model on a top surface of a microfluidic layer having channels that are open-top;
• seeding neuronal cells in a seeding chamber of a feed well provided in proximity of the microfluidic layer, the seeding chamber being in fluid communication with the channels of the microfluidic layer;
• supplying a cell culture medium to the channels via the seeding chamber of the feed well;
• and
• filing the reservoir with the cell culture medium up to a given level, wherein a proximity of the neuronal cells and the biological model enables interaction therebetween.

A cell culture device for use with a microfluidic layer for preparing a compartmentalized in vitro model, the cell culture device comprising:

• an insert insertable in a reservoir of a cell culture plate, the reservoir being configured to receive a culture medium fluid therein, the insert comprising:
• a bottom wall having a microfluidic layer-receiving portion on a top surface thereof;
• a microfluidic layer receivable directly or indirectly on the microfluidic layer-receiving portion of the reservoir of the cell culture plate, the microfluidic layer comprising channels for orienting axonal growth;
• an electrode provided in proximity of the microfluidic layer;
• and
• an upwardly extending feed well comprising a seeding chamber extending longitudinally therethrough and being configured to receive neuronal cells therein, the seeding chamber being configured to be in fluid communication with channels of the microfluidic layer.

A cell culture device for preparing a compartmentalized in vitro model using neuronal cells, the cell culture device comprising:

• a multi-well insert insertable in a reservoir of a cell culture plate, the reservoir being configured to receive a culture medium fluid therein, the multi-well insert comprising:
• a plurality of insert wells each comprising a bottom wall having a microfluidic layer-receiving portion on a top surface thereof;
• a microfluidic layer receivable directly or indirectly on the microfluidic layer-receiving portion of a corresponding one of the plurality of insert wells, the microfluidic layer comprising channels for orienting axonal growth;
• an electrode provided in proximity of the microfluidic layer;
• and
• an upwardly extending feed well provided in proximity of a corresponding one of the plurality of insert wells, the upwardly extending feed well comprising a seeding chamber extending longitudinally therethrough and being configured to receive the neuronal cells therein, the seeding chamber being configured to be in fluid communication with the channels of the microfluidic layer.

A cell culture device for preparing a compartmentalized in vitro model using neuronal cells, the cell culture device comprising:

• a cell culture plate defining a reservoir having a microfluidic layer-receiving portion on a top surface thereof;
• a microfluidic layer receivable directly or indirectly on the microfluidic layer-receiving portion of the reservoir of the cell culture plate, the microfluidic layer comprising channels for orienting axonal growth;
• an electrode provided in proximity of the microfluidic layer;
• a multi-well insert insertable in the reservoir of a cell culture plate onto the microfluidic layer, the multi-well insert comprising a plurality of insert wells that are bottomless;
• and
• an upwardly extending feed well provided in proximity of a corresponding one of the plurality of insert wells, the upwardly extending feed well comprising a seeding chamber extending longitudinally therethrough and being configured to receive the neuronal cells therein, the seeding chamber being configured to be in fluid communication with the channels of the microfluidic layer.