Polymer microfiltration devices, methods of manufacturing the same and the uses of the microfiltration devices

Abstract

A microfilter comprising a polymer layer formed from photo-definable dry film, and a plurality of apertures each extending through the polymer layer. A microfilter comprising two or more polymer layers formed from photo-definable dry film, and a plurality of apertures or open areas each extending through the polymer layer. Methods of forming apertures in one or more layers of photo-definable dry film are also disclosed. Filter holder designs and methods appropriate to hold microfilters to collect the rare cells and to perform of assays in the filter holder are provided. Microfiltration chip designs and methods appropriate to collect the rare cells and to perform assays in the microfluidic chips are provided. The invention also describes the use of the microfilter, filter holder and microfilter chips to collect rare cells from body fluids and perform assays, and these rare cells can be used for medical and biological research applications.

1 - 26 . (canceled) 
     
     
         27 . A filtration device comprising:
 an inlet layer including a first volume and a first inlet layer opening to said first volume;   a filter structure including a polymer filter layer having a first filter surface and a second filter surface diametrically opposite to said first filter surface; and   an outlet layer including a second volume and a first outlet layer opening to said second volume,   wherein said first filter surface is exposed to said first volume,   said second filter surface is exposed to said second filter volume, and   at least a filtered portion of a sample entering said first inlet layer opening, passes from said first volume to said second volume via said filter layer and exits said second volume via said first outlet layer opening.   
     
     
         28 . The filtration device of  claim 27 , further comprising:
 a top layer covering at least a portion of said first volume opposite said first surface of said filter layer; and   a base layer covering at least a portion of said second volume opposite said second surface of said filter layer.   
     
     
         29 . The filtration device of  claim 28 , wherein:
 said top layer includes a first top opening and a second top opening;   said first top opening communicatively connected with said first inlet top layer opening;   said top layer includes a top outlet layer opening communicatively connected with said second top opening;   said filter layer includes a first filter layer opening communicatively connected with said top outlet layer opening;   said sample interring said first volume via said first inlet layer opening; and   an unfiltered portion of said sample exits said top outlet opening connected with second top opening in the first volume, and   at least a filtered portion of a sample entering said first inlet layer opening, passes from said first volume to said second volume via said filter layer and exits said second volume via said first outlet layer opening.   
     
     
         30 . The filtration device of  claim 27 , wherein the polymer filter comprises photo-definable dry film. 
     
     
         31 . The filtration device of  claim 30 , wherein the photo-definable dry film comprises epoxy-based photo-definable dry film. 
     
     
         32 . The filtration device of  claim 27 , further comprising a coating of one or more elements on first filter surface of the first polymer layer. 
     
     
         33 . The filtration device of  claim 32 , wherein said elements include analyte recognition elements. 
     
     
         34 . The filtration device of  claim 27 , wherein said inlet layer includes a second inlet layer opening to said first volume. 
     
     
         35 . The filtration device of  claim 27 , wherein the filter structure comprises a plurality of filter layers in a stacked formation. 
     
     
         36 . A filtration method comprising:
 configuring a filtration device comprising:
 an inlet layer including a first volume and a first inlet layer opening to said first volume; 
 a filter structure including a polymer filter layer having a first filter surface and a second filter surface diametrically opposite to said first filter surface; and 
 an outlet layer including a second volume and a first outlet layer opening to said second volume, 
 wherein said first filter surface is exposed to said first volume, 
 said second filter surface is exposed to said second filter volume; and 
   passing a liquid sample into said first inlet layer opening whereby at least a filtered portion of a sample entering said first inlet layer opening passes through apertures in the filter from said first volume to said second volume via said filter layer and exits said second volume via said first outlet layer opening, and wherein the apertures are sized to essentially allow passage of a first type of component in the fluid and to substantially prevent passage of a second type of component in the fluid.   
     
     
         37 . The filtration method of  claim 36 , wherein said filtration device further comprises:
 a top layer covering at least a portion of said first volume opposite said first surface of said filter layer; and   a base layer covering at least a portion of said second volume opposite said second surface of said filter layer.   
     
     
         38 . The filtration method of  claim 37 , wherein:
 said top layer includes a first top opening and a second top opening;   said first top opening communicatively connected with said first inlet top layer opening;   said top layer includes a top outlet layer opening communicatively connected with said second top opening;   said filter layer includes a first filter layer opening communicatively connected with said top outlet layer opening;   said sample interring said first volume via said-first inlet layer opening; and   an unfiltered portion of said sample exits said top outlet opening connected with second top opening in the first volume, and   at least a filtered portion of a sample entering said first inlet layer opening, passes from said first volume to said second volume via said filter layer and exits said second volume via said first outlet layer opening.   
     
     
         39 . The method of  claim 36 , wherein the polymer filter comprises a photo-definable dry film filter. 
     
     
         40 . The method of  claim 36 , wherein the photo-definable dry film comprises epoxy-based photo-definable dry film. 
     
     
         41 . The method of  claim 36 , further comprising:
 performing, on the captured second component, one or more of identification, immunofluorescence staining, enumeration, cell lysis, fluorescence in situ hybridization, mRNA in situ hybridization, other molecular characterizations, immunohistochemistry, histopathological staining, flow cytometry, image analysis, enzymatic assays, gene expression profiling analysis, erythrocyte deformability, white blood cell reactions, efficacy tests of therapeutics, culturing of enriched cells, and therapeutic use of enriched rare cells, and separation from the microfilter.   
     
     
         42 . The method of  claim 36 , wherein the first filter surface includes a coating of one or more elements on at least one surface of the microfilter. 
     
     
         43 . The method of  claim 42 , wherein the elements comprise analyte recognition elements configured to capture components in the fluid. 
     
     
         44 . The filtration method of  claim 36 , wherein the filter structure comprises a plurality of filter layers in a stacked formation. 
     
     
         45 . A method of configuring a filtration device comprising:
 providing an inlet layer including a first volume and a first inlet layer opening to said first volume;   providing a filter structure including a polymer filter layer having a first filter surface and a second filter surface diametrically opposite to said first filter surface; and   providing an outlet layer including a second volume and a first outlet layer opening to said second volume,   wherein said first filter surface is exposed to said first volume,   said second filter surface is exposed to said second filter volume, and   at least a filtered portion of a sample entering said first inlet layer opening, passes from said first volume to said second volume via said filter layer and exits said second volume via said first outlet layer opening.   
     
     
         46 . The method of  claim 45 , further comprising:
 providing a top layer covering at least a portion of said first volume opposite said first surface of said filter layer; and   providing a base layer covering at least a portion of said second volume opposite said second surface of said filter layer.   
     
     
         47 . The method of  claim 36 , wherein the liquid comprises a body fluid comprising at least one of the group consisting of blood, urine, cerebral spinal fluid and saliva. 
     
     
         48 . The method of  claim 36 , wherein the liquid comprises water. 
     
     
         49 . The method of  claim 36 , wherein the liquid contains disbursed components from bone marrow, tumor tissue, and other tissue. 
     
     
         50 . The method of  claim 36 , wherein said second component comprises at least one of circulating tumor cells, circulating endothelial cells, stem cells, stromal cells, epithelial cells, non-hematopoietic cells, fetal cells, nucleated red blood cells, trophoblstic cells, macrophages, circulating cancer associated macrophage-like cells, epithelial-mesenchymal transition cells, blood cells, processed tissue sample cells, white blood cells, T-cells, B-cells, and tumor cells from bone marrow. 
     
     
         51 . The method of  claim 36 , wherein said second component comprises at least one of leukocytes, T-cells and B-cells, and the liquid sample is blood.