Extracorporeal Fluidic Device for Collecting Circulating Tumor Cells and Method of Use Thereof

Abstract

A device can be used to retain circulating tumor cells (CTCs). The device can include a cross-flow module with a retentate channel and a permeate channel. A filter in the cross-flow module can separate the retentate channel from the permeate channel. The filter can be constructed such that CTCs are retained in the retentate channel while other cells can pass through the filter into the permeate channel. A recirculation channel can direct a flow from an outlet of the retentate channel back to an inlet of the retentate channel to thereby concentrate CTCs in the retentate flow.

1 . A device for retaining circulating tumor cells (CTCs), comprising:
 a retentate channel;   a permeate channel;   a first filter separating the retentate channel from the permeate channel and constructed such that CTCs are retained in the retentate channel while other cells pass through the first filter to the permeate channel; and   a recirculation channel that directs a flow from an outlet of the retentate channel to an inlet of the retentate channel.   
     
     
         2 . The device of  claim 1 , wherein the recirculation channel further comprises a treatment element to collect or concentrate CTCs. 
     
     
         3 . The device of  claim 1 , wherein the recirculation channel further comprises a recirculation pump. 
     
     
         4 . The device of  claim 2 , wherein the treatment element comprises a second filter for separating CTCs from the retentate fluid. 
     
     
         5 . The device of  claim 4 , wherein the second filter is constructed such that white blood cells in the retentate fluid can pass through the treatment element. 
     
     
         6 . The device of  claim 4 , wherein the first filter and/or the second filter is provided with an anti-EPCAM antibody, anti-EFGR antibody, or other antibody capable of binding CTCs. 
     
     
         7 . The device of  claim 2 , wherein the treatment element is configured to expose white blood cells to concentrated CTCs, thereby bringing the CTCs and white blood cells in close contact with each other to stimulate a patient's immune system to attack CTCs. 
     
     
         8 . The device of  claim 7 , wherein the treatment element comprises additional cytokines to stimulate and mature the white blood cells. 
     
     
         9 . The device of  claim 1 , wherein the retentate channel has a tapered cross-section that maintains a constant shear rate of the retentate fluid flow. 
     
     
         10 . The device of  claim 1 , wherein the permeate channel has a tapered cross-section that maintains a constant transmembrane pressure across the CTC filter. 
     
     
         11 . The device of  claim 1 , wherein the device provides a flow of blood from the permeate channel to a patient is at least 80% of a flow of unfiltered blood from the patient to the device. 
     
     
         12 . The device of  claim 1 , wherein the filter has a smooth, flat, polished surface. 
     
     
         13 . The device of  claim 12 , wherein the filter has regularly spaced straight pores with an aspect ratio of no more than ten. 
     
     
         14 . The device of  claim 13 , wherein the filter has regularly spaced straight pores with an aspect ratio of no more than two. 
     
     
         15 . The device of  claim 1 , further comprising fluidic connections to a patient's blood stream via a vascular access. 
     
     
         16 . The device of  claim 1 , wherein a module forming the retentate and permeate channels on opposite sides of the first filter has a rhomboid shape in profile. 
     
     
         17 . The device of  claim 1 , wherein the retentate fluid flow has a mean shear rate of at least about 100 s −1 . 
     
     
         18 . The device of  claim 1 , wherein the permeate channel and/or retentate channel are configured to maintain a constant ratio of transmembrane pressure and shear rate along the first filter. 
     
     
         19 . The device of  claim 1 , wherein the permeate channel has a height between 200 μm and 500 μm, and the retentate channel has a height between 50 μm and 500 μm.