Capillary perfused bioreactors with multiple chambers

• US 8,003,378 B2
• Filed: 03/05/2009
• Issued: 08/23/2011
• Est. Priority Date: 08/27/2002
• Status: Expired due to Fees

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Lin, Charles P., Hofmeister, William H., Prokop, Ales, Reiserer, Randall S., Chung, Chang Y., Haselton, Frederick R., Stremler, Mark A., Cliffel, David E., McCawley, Lisa J., Baudenbacher, Franz J., LeBoeuf, Eugene, Wikswo, John P.
• Primary Examiner(s): LAM, ANN Y
• Application Number:
  US12/398,825
• Publication Number:
  US 20090215654A1
• Time in Patent Office: 901 Days
• Field of Search: None
• US Class Current: 435/289.1
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/10 Means to control humidity and/or other gases
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 29/10 Perfusion

Abstract

A bioreactor for cultivating living cells in a liquid medium. In one embodiment of the present invention, the bioreactor includes a first substrate having a first surface, an opposite second surface and edges. The bioreactor further includes a second substrate having a first surface and an opposite second surface, defining a cavity with a bottom surface, where the bottom surface is located therebetween the first surface and the second surface. The first surface of the first substrate is received by the second surface of the second substrate to cover the cavity so as to form a channel for receiving cells and a liquid medium. In forming the bioreactor, the channel is sized to allow the growth of a layer of cells on a biocompatible coating layer and a flow of liquid in the channel. The flow of liquid is controlled so as to provide a known shear force to the layer of cells. The flow of liquid can be further controlled so as to provide an environment that simulates a vascular space in the channel.

Claims

1. A bioreactor comprising:

(i) a first substrate having a first surface, an opposite second surface and edges;

(ii) a second substrate having a first surface and an opposite second surface, defining a cavity with a bottom surface, wherein the bottom surface is located therebetween the first surface of the second substrate and the second surface of the second substrate, and wherein the first surface of the first substrate is received by the second surface of the second substrate to cover the cavity so as to form a channel for receiving biological cells and a liquid medium;

(iii) a recess formed in the second substrate with a bottom surface and in fluid communication with the channel; and

(iv) a barrier positioned for covering the recess so as to form an outer chamber, wherein the barrier has a porosity to allow the channel and the outer chamber to be in fluid communication and control the movement of at least one predetermined type of biological cells between the channel and the outer chamber, and wherein at least a portion of the barrier is arranged substantially perpendicular to the first surface of the first substrate.

2. The bioreactor of claim 1, wherein the second substrate further defines a first opening and an opposite, second opening adapted for allowing a flow of liquid to be introduced into the channel through the first opening and away from the channel through the second opening substantially along a first direction.

3. The bioreactor of claim 2, further comprising a biocompatible coating layer applied to the interior surfaces of the second substrate around the channel.