Continuous perfusion bioreactor system

摘要

Systems and methods for containing and manipulating liquids, including vessels and unit operations or components of cell culture, cell containment, bioreactor, and/or pharmaceutical manufacturing systems, are provided. In certain embodiments, such vessels and unit operations are directed to continuous perfusion reactor or bioreactor systems and may include one or more disposable components. For instance, in one aspect, a system includes an apparatus in the form of a bioreactor for harvesting cells which produce one or more products. The apparatus may include a disposable, collapsible bag adapted for containing a liquid, the collapsible bag in fluid communication with a liquid-solids (e.g., cell) separation device. For example, an outlet of the collapsible bag may be connected to an inlet of the separation device, and an outlet of the separation device may be connected to an inlet of the collapsible bag for recycle. Accordingly, after separating the cells from the liquid in the separation device, the cells can be flowed back into the collapsible bag where they can be re-harvested. Meanwhile, product contained in the liquid can be collected in a separate container. The efficiency of product formation in such a system may be enhanced by using mixing systems described herein.

主权项

1. A continuous perfusion bioreactor system, comprising:
a first apparatus, comprising:
a first disposable, flexible or collapsible bag adapted for containing a liquid and configured for use as a disposable continuous perfusion bioreactor, the first disposable, flexible or collapsible bag including a first inlet, a first outlet, and a base plate that is attached to the first disposable, flexible or collapsible bag;an impeller associated with the base plate;a first reusable support structure adapted for surrounding and supporting the first collapsible bag; anda second apparatus comprising a liquid-solids separation device and a second disposable, flexible or collapsible bag adapted for containing a liquid, the liquid-solids separation device in fluid communication with the first disposable, flexible or collapsible bag, and first apparatus, the liquid-solids separation device including a liquid-solids separation device inlet, and a liquid-solids separation device outlet, wherein the second apparatus is disposed external to the first disposable collapsible bag,and the first outlet of the first disposable collapsible bag is connected to in fluid communication with the liquid-solids separation device inlet andthe liquid-solids separation device outlet is in connected to the first inlet of the first disposable collapsible bag; andwherein the liquid-solids separation device is configured to receive a first liquid comprising a first concentration of a component from the first disposable collapsible bag apparatus and to deliver a second liquid comprising a second concentration of the component to the first disposable collapsible bag apparatus, wherein the first and second concentrations are the same or different.