Microcolumn-platform based array for high-throughput analysis

Abstract

A device and methods for performing biological or chemical analysis is provided. The device includes an array of three-dimensional microcolumns projecting away from a support plate. Each microcolumn has a relatively planar, first surface remote from the support plate. An array of multiple, different biological materials may be attached to the first surface. The device, when used in combination with existent micro-titer well plates, can improve efficiency of binding assays using microarrays for high-throughput capacity.

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       56 . An assembly suitable for performing a biological or chemical assay, the assembly comprises: 
 a) an article having (1) a support structure; (2) a plurality of microcolumns projecting away from said support structure; (3) each of said microcolumns having a first surface remote from said support structure and at least a second surface;    b) a microtiter plate having a corresponding number of wells into which each of said microcolumns may be inserted; and    c) a plurality of biological or chemical materials immobilized on either: (1) the first surface of each microcolumn; (2) on an interior surface of each of said wells; or (3) both.    
   
   
       57 . The assembly according to  claim 56 , further comprising a physical adaptor for holding said microcolumns when imaging said biological materials.  
   
   
       58 . The assembly according to  claim 56 , wherein said plurality of microcolumn is arranged in a strip.  
   
   
       59 . The assembly according to  claim 58 , wherein said strip of microcolumns number from 6 to 48 individual microcolumns.  
   
   
       60 . The assembly according to  claim 56 , wherein at least one well in the microtiter plate has a spacer located around a periphery of a bottom wall of the well, wherein the spacer maintains a capillary space between the bottom of the well and the first surface of the microcolumn.  
   
   
       61 . The assembly according to  claim 56 . further comprising a second tray for performing common washes.  
   
   
       62 . The assembly according to  claim 56 , wherein said micro-titer plate have wells with bottom walls that are both hydrophobic along a periphery of the bottom wall and hydrophilic in a center area.  
   
   
       63 . The assembly according to  claim 56 , wherein said first surface is orthogonally oriented to the second surface.  
   
   
       64 . The assembly according to  claim 56 , wherein said biological or chemical materials comprise: DNA, RNA, oligonucleotides, plasmids, peptides, proteins, lipids, membranes, chemical molecules, pharmaceutical compounds, viral particles, cells, sub-cellular components, and cellular products.  
   
   
       65 . The assembly according to  claim 56 , wherein said biological materials comprises cDNA or oligonucleotides.  
   
   
       66 . The assembly according to  claim 56 , wherein said biological materials comprises proteins or peptides.  
   
   
       67 . The assembly according to  claim 56 , wherein said biological materials comprises chemical molecules or pharmaceutical compounds.  
   
   
       68 . The assembly according to  claim 56 , wherein one kind of biological or chemical material is immobilized to either said first surface or said interior surface and another kind to the opposing other surface  
   
   
       69 . The assembly according to  claim 68 , wherein said a protein array is positioned on either the first surface or interior surface, and a nucleic acid array is on the opposing other surface.  
   
   
       70 . The assembly according to  claim 56 , wherein said multiple different biological materials are arranged as a rectilinear array.  
   
   
       71 . The assembly according to  claim 56 , wherein a plurality of said microcolumns is arranged in an array.  
   
   
       72 . The assembly according to  claim 71 , wherein said microcolumns are arranged in a microplate plate footprint.  
   
   
       73 . The assembly according to  claim 72 , wherein said microcolumns are arrayed in either a 96-, 384-, or 1536-matrix.  
   
   
       74 . The assembly according to  claim 56 , wherein said microcolumn has a monolithic structure.  
   
   
       75 . The assembly according to  claim 56 , wherein said microcolumn has a geometry selected from one of the following: a cylinder, a rectangular solid, an hour glass, or an inverted frusto-cone.  
   
   
       76 . The assembly according to  claim 56 , wherein said first surface is substantially planar.  
   
   
       77 . The assembly according to  claim 56 , wherein said first surface is oriented orthogonally to the second surface.  
   
   
       78 . The assembly according to  claim 56 , wherein said microcolumn has a cross-sectional dimension of about 10 cm or smaller.  
   
   
       79 . The assembly according to  claim 56 , wherein said microcolumn has a cross-sectional dimension of about 0.2 mm or larger.  
   
   
       80 . The assembly according to  claim 56 , wherein said microcolumn has a cross-sectional dimension in the range from about 0.4 mm to about 5.5 mm.  
   
   
       81 . The assembly according to  claim 56 , wherein said microcolumn has a horizontal cross-sectional shape selected from the group consisting of: circles, squares, rectangles, ovals, triangles, and polygons.  
   
   
       82 . The assembly according to  claim 56 , wherein said microcolumn is made of a material selected from a glass, polymeric, metallic, ceramic, or composite material.  
   
   
       83 . The assembly according to  claim 82 , wherein said first surface is has a material selected from: an amino propylsilane-treated glass, quartz, fused silica.  
   
   
       84 . The assembly according to  claim 82 , wherein said first surface is has a material selected from: polypropylene, polystyrene, nylon filter.  
   
   
       85 . The assembly according to  claim 82 , wherein said first surface is has a material selected from: gold, silver, platinum, chromium, and silicon.  
   
   
       86 . The assembly according to  claim 56 , wherein said microcolumn has a hollow cavity extending from said support structure, through said microcolumn, to said first surface.  
   
   
       87 . The assembly according to  claim 86 , wherein said hollow cavity comprises an inlet port, an outlet port, and a microchannel connecting the inlet and outlet ports.  
   
   
       88 . The assembly according to  claim 87 , wherein said microchannel has a diameter of about 500 μm or less.  
   
   
       89 . The assembly according to  claim 56 , wherein said microcolumn has a hollow cavity that extends about 99.5% or less through the length of a shaft of said microcolumn and is capable of receiving a fiber optical imaging component.  
   
   
       90 . The assembly according to  claim 56 , wherein said device further comprises: 
 a) a plurality of micropins located on said first surface of said microcolumn,    b) each of said micropins has either: 
 1) a hydrophilic wetting surface, and at least a hydrophobic non-wetting second surface, or  
 2) a roughened surface that entraps fluids with multiple fluid contact angles, and having a different biological material attached to each of said wetting surface or said roughened surface.  
   
   
   
       91 . The assembly according to  claim 90 , wherein said micropins are arranged in an array.  
   
   
       92 . The assembly according to  claim 90 , wherein said micropins have a cross section dimension generally between about 1 μm and about 4 mm.  
   
   
       93 . The assembly according to  claim 90 , wherein said micropins are made of a material selected from a glass, polymeric, metallic, ceramic, or composite material.  
   
   
       94 . A method for performing an assay, the method comprises: 
 a) providing a device having at a number of microcolumns projecting away from a support structure, each of said microcolumns having a first surface remote from said support structure and at least a second surface;    b) providing a microtiter plate with a number of wells corresponding to said number of microcolumns;    c) immobilizing an array of multiple samples of biological material on either: 1) the first surface of each microcolumn; 2) on an interior surface of each of said wells; or 3) both;    d) inverting said device, whereby the first surface of each microcolumn is oriented toward the interior surface of each well;    e) engaging said microcolumns with said wells;    f) introducing an assay reagent solution;    g) performing an assay.    
   
   
       95 . The method according to  claim 94 , wherein the method further comprises: introducing said assay solution through a fluid conduit extending through said microcolumn.  
   
   
       96 . The method according to  claim 94 , wherein the method further comprises: a) creating a capillary space between the first surface of each microcolumn and the interior surface of each well; and b) agitating said device to react said biological material in said assay solution.  
   
   
       97 . The method according to  claim 94 , wherein the method further comprises: removing said microcolumn from said well; and imaging said first surface.  
   
   
       98 . The method according to  claim 97 , wherein the method further comprises: 
 a) washing said microcolumns in a second micro-titer plate;    b) drying said first surface; and    c) studying and quantifying biological analytes bound to the array on the first surface of said microcolumns.    
   
   
       99 . The method according to  claim 98 , wherein for imaging said first surface, a physical adaptor is fitted to said microcolumn and support structure.  
   
   
       100 . The method according to  claim 99 , wherein said physical adaptor is fabricated to receive and hold said microcolumns.  
   
   
       101 . The method according to  claim 94 , wherein said device further comprises an array of micropins located on said first surface of said microcolumn, said micropins having a first surface and at least a second surface, and having biological material attached to said first surface.  
   
   
       102 . The method according to  claim 94 , wherein said biological material comprises: DNA, RNA, oligonucleotides, plasmids, peptides, proteins, lipids, membranes, chemical molecules, pharmaceutical compounds, viral particles, cells, sub-cellular components, and cellular products.  
   
   
       103 . A method for performing biological analysis, the method comprises: 
 a) providing a device comprising: 
 1) a support structure; a number of microcolumns located on a planar surface of said support structure; each of said microcolumns having a first surface remote from said support structure and at least a second surface; and an array of multiple biological materials, selected from the group consisting of DNA, RNA, oligonucleotides, plasmids, peptides, proteins, lipids, membranes, chemical molecules, viral particles, cells, sub-cellular components, and cellular products, deposited in an orderly array on each first surface;  
   b) inverting said device, such that said first surface of each microcolumn is oriented downwards;    c) inserting each microcolumn into a well of a microtiter plate, said well containing an assay solution;    d) agitating said device to react said biological material with said assay solution;    
   
   
       104 . The method according to  claim 103 , wherein the method further comprises: 
 a) withdrawing said device;    b) washing said device in a second microtiter plate having either a number of microtiter wells or one common reservoir;    c) drying said first surface; and    d) studying and quantifying biological analytes bound to the array on the first surface of said microcolumns.    
   
   
       105 . A biosensor device comprising an planar support structure having an array of microcolumns extending therefrom, each of said microcolumns having a planar first surface and at least a second surface, having a grating integrated in each first surface, and having a set of biological materials arranged and disposed on said first surface in a rectilinear fashion.  
   
   
       106 . The biosensor device according to  claim 105 , wherein said first surface has a waveguide coating.  
   
   
       107 . The biosensor device according to  claim 105 , wherein each of said microcolumns is a monolithic structure.  
   
   
       108 . The biosensor device according to  claim 105 , wherein each of said microcolumns has a hollow cavity extending from said support structure, through said microcolumn, to said first surface.  
   
   
       109 . The biosensor device according to  claim 108 , wherein said hollow conduit comprises an inlet port, an outlet port, and a microchannel connecting the inlet and outlet ports.  
   
   
       110 . The biosensor device according to  claim 109 , wherein said microchannel has a diameter of about 500 μm or less.  
   
   
       111 . The biosensor device according to  claim 110 , wherein each of said microcolumns has a hollow cavity that extends about 99.5% or less through the length of a shaft of said microcolumn and is capable of receiving a fiber optical imaging component.