Membrane microfluidic device for controlled flux delivery into a flow stream

Purpose: Microfluidic devices allow the controlled delivery of solutes into a flow stream.  Using a membrane placed between two fluidic channels, the solute delivery may include either a diffusive flux, convective flux, or intermediate, based upon control of the pore Peclet number (Neeves, 2010; Neeves, 2008).

Microfluidic device for control delivery of solutes into a flow stream. (A) The device consisted of two perpendicular channels in PDMS separated by a polycarbonate membrane. The two PDMS layers are reversibly sealed using vacuum assisted bonding. (B) At the intersection of the two channels, the flux of the agonist molecules was controlled by the pore size and transmembrane pressure. The transmembrane pressure was manipulated by varying the relative flow rate (Q1/Q2) between the top and bottom channels. (C) Electron micrograph of the bottom channel and posts in the vacuum chamber, which provided mechanical support during operation.

Microfluidic device for control delivery of solutes into a flow stream. (A) The device consisted of two perpendicular channels in PDMS separated by a polycarbonate membrane. The two PDMS layers are reversibly sealed using vacuum assisted bonding. (B) At the intersection of the two channels, the flux of the agonist molecules was controlled by the pore size and transmembrane pressure. The transmembrane pressure was manipulated by varying the relative flow rate (Q1/Q2) between the top and bottom channels. (C) Electron micrograph of the bottom channel and posts in the vacuum chamber, which provided mechanical support during operation.

Method of Fabrication/Use: This sandwich type device involves the placement of a transparent track-etched polycarbonate membrane between two distinct PDMS devices each with a 100 mm x 100 mm channel.  A post array in the bottom device supports the vacuum chamber and the membrane.  Calibration studies with luciferase confirmed control of molecular flux through the membrane.

Results: The Diamond Lab has used this device to study extreme ADP delivery into a blood stream to activate platelets near the boundary layer {Neeves, 2008 #41; Neeves, 2008 #43}.  At the lowest ADP flux (1.5 × 10−18 mol μm−2 s−1), we observed little to no aggregation. At the higher fluxes, we observed monolayer (2.4 × 10−18 mol μm−2 s−1) and multilayer (4.4 × 10−18 mol μm−2 s−1) aggregates of platelets and found that the platelet density within an aggregate increased with increasing ADP flux. A similar approach was used to deliver thrombin into fibrinogen flow to study fibrin polymerization under flow conditions {Neeves, 2010 #42}. At a thrombin flux of 10-12 nmol/mm2-s, both fibrin deposition and fiber thickness decreased as the wall shear rate increased from 10 to 100 s-1. Direct measurement and transport-reaction simulations at 12 different thrombin flux-wall shear rate conditions demonstrated that two dimensionless numbers, the Peclet number (Pe) and the Damkohler number (Da), defined a state diagram to predict fibrin morphology.

References

Neeves KB, Diamond SL. A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood. Lab Chip May 2008; 8 (5): 701-709.

Neeves KB, Illing DA, Diamond SL. Thrombin flux and wall shear rate regulate fibrin fiber deposition state during polymerization under flow. Biophys J Apr 7 2010; 98 (7): 1344-1352.

Neeves KB, Maloney SF, Fong KP, Schmaier AA, Kahn ML, Brass LF, Diamond SL. Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear-resistance of platelet aggregates. J Thromb Haemost Dec 2008; 6 (12): 2193-2201.

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