Multi-well microfiltration apparatus

Abstract

The present invention provides multi-well plates and column arrays in which samples (e.g., cell lysates containing nucleic acids of interest, such as RNA) can be analyzed and/or processed. In one embodiment, the microfiltration arrangement is a multilayer structure, including (i) a column plate having an array of minicolumns into which samples can be placed, (ii) a discrete filter element disposed in each minicolumn, (iii) a drip-director plate having a corresponding array of drip directors through which filtrate may egress, and (iv) a receiving-well plate having a corresponding array of receiving wells into which filtrate can flow. The invention provides multi-well microfiltration arrangements that are relatively simple to manufacture and that overcome many of the problems associated with the prior arrangements relating to (i) cross-contamination due to wicking across a common filter sheet or (ii) individual filter elements entrapping sample constituents within substantial dead volumes. Further, the invention provides multi-well microfiltration arrangements that adequately support discrete filter elements disposed in the wells without creating substantial preferential flow. Additionally, the invention provides multi-well microfiltration arrangements that avoid cross-contamination due to aerosol formation, pendent drops and/or splattering. Other disclosed features of the invention provide for the automated covering or heat-sealing of filtrate samples separately collected in an array of wells.

It is claimed:  
     
         1 . A method of sealing a heat-sealable sheet over an array of wells held in a collection tray, each of said wells having an open upper end, said method comprising: 
 picking up a heat-sealable sheet; placing the sheet over said open upper ends; and pressing a conformable heated surface against said sheet, from a side opposite said collection tray, with sufficient pressure such that said sheet is heat-sealed to said collection tray over said open upper ends.    
     
     
         2 . The method of  claim 1 , wherein said conformable heated surface is pressed against said sheet using a plurality of spaced-apart elongated rods, disposed substantially normal to an upper surface of said collection plate.  
     
     
         3 . The method of  claim 2 , wherein the rods depend from a support structure positioned above the collection plate.  
     
     
         4 . The method of  claim 1 , wherein the heat-sealable sheet is optically clear.  
     
     
         5 . The method of  claim 1 , wherein a surface of the open upper end has raised features.  
     
     
         6 . The method of  claim 5 , wherein the conformable heated surface, during the step of pressing the conformable heated surface, contacts all points on the surface of the open upper end.  
     
     
         7 . The method of  claim 4 , further comprising: prior to said placing step, loading a plurality of said wells with respective samples each containing at least one nucleic acid, and, subsequent to said pressing step, subjecting said samples to conditions suitable to amplify said at least one nucleic acid by polymerase chain reaction (PCR).  
     
     
         8 . The method of  claim 7 , further comprising measuring the generation of nucleic-acid products resulting from said PCR in real-time through said sheet.  
     
     
         9 . The method of  claim 5 , wherein said tray includes an upper surface, with said wells formed therein and depending therefrom, and wherein said well upper ends define ridges projecting above said tray upper surface.  
     
     
         10 . The method of  claim 1 , wherein the sealing of heat sealable sheet occurs in a semi-automated or automated fashion.  
     
     
         11 . The method of  claim 1 , wherein the array of wells is a plate for use in a scientific or laboratory instrument, wherein the plate has a plurality of wells disposed in the plate.  
     
     
         12 . The method of  claim 1 , wherein the open upper end has a compliant, resilient surface.  
     
     
         13 . A system comprising: 
 at least one heat sealable sheet;    a bin adapted to hold a plurality of heat sealable sheets; and    an array of wells,    wherein the sealing of heat sealable sheets from the bin over the array of wells occurs in a semi-automated or automated fashion.    
     
     
         14 . The system of  claim 13 , wherein the heat sealable sheet is optically clear.  
     
     
         15 . The system of  claim 13 , wherein the array of wells is a plate for use in a scientific or laboratory instrument, wherein the plate has a plurality of wells disposed in the plate.  
     
     
         16 . A system comprising: 
 an array of wells;    a heat sealable means for sealing an array of wells; and    a holding means to hold a plurality of heat sealable means, wherein the heat sealable means held in the holding means is adapted to be sealed to the array of wells in semiautomatic or automatic fashion.