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.

We claim: 
     
         1 . 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 single polymer filter layer with uniform thickness formed from negative photo-definable dry film having a first filter surface and a second filter surface diametrically opposite to said first filter surface, and a plurality of apertures each extending through the polymer filter layer, said filter structure having flexibility allowing for disposing on a roll and unrolling; 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 volume,   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,   said filter structure retaining on said first filter surface at least an unfiltered portion of said sample entering said first inlet layer, and   one of:
 said inlet layer is transparent for visual analysis of said unfiltered portion retained on said first filter, 
 said inlet layer is transparent and said outlet layer is transparent or opaque, or 
 said inlet layer and said out let layer are essentially non-fluorescent for fluorescence analysis of said unfiltered portion retained on said first filter surface. 
   
     
     
         2 . The filtration device of  claim 1 , 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.   
     
     
         3 . The filtration device of  claim 2 , wherein:
 said top layer includes a first top opening and a second top opening;   said first top opening communicatively connected with said first inlet layer opening;   said inlet layer further includes a second outlet layer opening communicatively connected with said second top opening;   said polymer filter layer includes a third outlet layer opening communicatively connected with said second outlet layer opening and with said first outlet layer opening;   said sample entering said first volume via said first top opening; and   said filtered portion of said sample entering said first inlet layer opening, passing from said first volume to said second volume via said filter layer, and exiting said second volume via said second top opening.   
     
     
         4 . The filtration device of  claim 1 , wherein the photo-definable dry film comprises epoxy-based photo-definable dry film. 
     
     
         5 . The filtration device of  claim 1 , further comprising a coating of one or more elements on first filter surface of the first polymer layer. 
     
     
         6 . The filtration device of  claim 5 , wherein said elements include analyte recognition elements. 
     
     
         7 . 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 single polymer filter layer with uniform thickness formed from negative photo-definable dry film having a first filter surface and a second filter surface diametrically opposite to said first filter surface, and a plurality of apertures each extending through the polymer filter layer, said filter structure having flexibility allowing for disposing on a roll and unrolling; 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 volume,   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,   said inlet layer includes a second inlet layer opening to said first volume, and said filter structure not retaining on said first filter surface at least said unfiltered portion of said sample entering said first inlet layer opening and exiting said second inlet layer opening, and   one of:
 said inlet layer is transparent for visual analysis of said unfiltered portion retained on said first filter, 
 said inlet layer is transparent and said outlet layer is transparent or opaque, or 
 said inlet layer and said out let layer are essentially non-fluorescent for fluorescence analysis of said unfiltered portion retained on said first filter surface. 
   
     
     
         8 . The filtration device of  claim 1 , wherein the filter structure comprises a plurality of filter layers in a stacked formation 
     
     
         9 . A filter holder comprising:
 an inlet unit including a first volume and a first opening to said first volume; and   an outlet unit including a second volume for accommodating a filter structure removably configured therein, and a second opening to said second volume,   wherein   said filter structure includes a single polymer filter layer with uniform thickness formed from negative photo-definable dry film having a first filter surface and a second filter surface diametrically opposite to said first filter surface, and a plurality of apertures each extending through the polymer filter layer, and   said first and second openings are at opposite ends when said inlet unit is secured to said outlet unit, and said filter structure is exposed for observation of filtered substance collected on said filter structure and for performing an essay on said filtered substance within said first volume through said first opening.   
     
     
         10 . The filter holder of  claim 9 , further comprising a nut configured to removably attach to said outlet unit and removably secure said inlet unit to said outlet unit,
 wherein said first opening is exposed through said nut   
     
     
         11 . The filter holder of  claim 9 , wherein said first volume accommodates a reagent therein when placed therein. 
     
     
         12 . The filter holder of  claim 9 , further comprising a first gasket disposed in said second volume with respect to said filter structure,
 wherein said gasket includes a third opening aligned with said first opening and said second opening.   
     
     
         13 . The filter holder of  claim 9 , further comprising a plurality of gaskets disposed in said second volume with respect to said filter structure,
 wherein each of said gaskets includes a gasket opening aligned with said first opening and said second opening.   
     
     
         14 . The filter holder of  claim 13 , wherein at least one of said gaskets is configured between said inlet unit and said filter structure, or between said filter structure and said outlet unit. 
     
     
         15 . The filter holder of  claim 13 , wherein said filter structure is configured between at least two of said gaskets. 
     
     
         16 . The filter holder of  claim 13 , wherein said filter structure comprises one or more essentially flat layers. 
     
     
         17 . The filter holder of  claim 9 , wherein said outlet unit is configured to facilitate attachment of an outlet container at said second opening. 
     
     
         18 . The filter holder of  claim 9 , wherein said second opening of said outlet unit comprises an outlet output for attachment of a male or female input connection of a syringe or vacutainer holder. 
     
     
         19 . The filter holder of  claim 9 , wherein said inlet unit further comprises an inlet adapter including an adapter input for attachment of a sample input container thereto and an adapter output in communication with said first volume allowing passage of at least a portion of a sample material from said sample input container to said first volume. 
     
     
         20 . The filter holder of  claim 2 , wherein said inlet unit further comprises an inlet adapter including an adapter input for attachment of a sample input container thereto and an adapter output in communication with said first volume allowing passage of at least a portion of a sample material from said sample input container to said first volume,
 wherein said adapter input extends through said nut whereby said first opening is exposed through said nut.   
     
     
         21 . The filter holder of  claim 19 , wherein said sample input container comprises a syringe having a male or a female output connection, and said adapter input is configured for attachment of said male or female output connection of said syringe. 
     
     
         22 . The filter holder of  claim 9 , wherein:
 said inlet unit comprises essentially cylindrical first inner surface and first outer surface; and   said outlet unit comprises essentially cylindrical second inner surface and second outer surface.   
     
     
         23 . The filter holder of  claim 22 , wherein at least one of:
 said first inner surface and first outer surface are concentric; and   said second inner surface and second outer surface are concentric.   
     
     
         24 . The filter holder of  claim 22 , wherein at least one of:
 said first inner surface and said second inner surface are essentially concentric when said inlet unit and said outlet unit are secured; and   said first outer surface and said second outer surface are essentially concentric when said inlet unit and said outlet unit are secured.   
     
     
         25 . The filter holder of  claim 22 , wherein at least one of:
 said first inner surface and said second inner surface comprises at least one essentially equal cross sectional diameter; and   said first outer surface and said second outer surface comprises at least one essentially equal cross sectional diameter.   
     
     
         26 . The filter holder of  claim 1 , wherein said filter structure comprises:
 a polymer layer formed from epoxy-based photo-definable material; and   a plurality of apertures each extending through the polymer layer.   
     
     
         27 . A method of performing an essay comprising:
 positioning a microfilter into a filter folder as claimed in  claim 9 ;   selectively placing a filter into an outlet unit, the outlet unit including a seat for removably accommodating said filter or a gasket, and a second opening therethrough to facilitate attachment of an output container thereto;   removably placing said gasket onto said filter or under said filter, wherein a diameter of said filter is essentially equal to an outer diameter of said gasket and an outer diameter of said seat;   removably placing an inlet unit onto said filter when said gasket is under said filter, or removably placing said inlet unit onto said gasket when said gasket is on said filter, said inlet unit including a first opening opposite to said second opening;   installing a nut onto said outlet unit to removably secure said inlet unit, said filter, and said gasket with said outlet unit and said nut, said first opening being exposed through said nut,   wherein said first and second openings are diametrically opposite when said inlet is secured to said outlet unit, and said filter structure is exposed for observation or manipulation through said first opening;   passing a sample through said microfilter; and   performing an assay of material collected on said microfilter without removing said microfilter from said filter holder.   
     
     
         28 . A container comprising:
 a third volume for accommodating a fluid;   an inlet opening to an interior of said third volume; and   an outlet opening configured to accommodate a connection to a filter holder as claimed in  claim 9 ,   wherein said outlet opening connects to said first opening of said filter holder.   
     
     
         29 . The container of  claim 28 , further comprising an inlet adapter configured to communicatively connect said outlet opening to said first opening of said filter holder. 
     
     
         30 . A system comprising:
 a filter holder as claimed in  claim 9 ;   an input container comprising
 an input container volume for accommodating a fluid, 
 a first input container opening to an interior of said input container volume for placing a sample into said input container volume, and 
 a second input container opening configured to accommodate a connection to said first opening of said inlet unit; and 
   an outlet container comprising
 an output container volume for accommodating a fluid, 
 a first output container opening to an interior of said volume, said first output container opening configured to accommodate a connection to said second opening of said outlet unit, and 
 a second output container opening to an interior of said output container volume to selectively release said sample; 
   wherein, when a suction force is applied at said second output container opening, said sample passes from said input container to said output container through said first and second openings of said filter holder via said filter structure to collect said filtered substance on said filter structure.   
     
     
         31 . The system as claimed in  claim 30 , wherein said output container is configured as one of syringe pump or a vacutainer. 
     
     
         32 . A system comprising:
 a filter holder as claimed in  claim 9 ;   a needle selectively attachable to said filter holder at said first opening of said inlet unit; and   a vacutainer holder comprising
 a first vacutainer opening for insertion of a vacutainer, and 
 a second vacutainer opening in communication with said second opening of said outlet unit, 
   
       wherein, when a vacutainer is inserted into the vacutainer holder, a suction force is applied at said second vacutainer opening, whereby said sample passes via said needle to said vacutainer through said first and second openings of said filter holder via said filter structure to collect said filtered substance on said filter structure.