Coating process for microfluidic sample arrays

Abstract

A differentially coated device for conducting a plurality of nano-volume specified reactions, the device comprising a platen having at least one exterior surface modified to a specified physicochemical property, a plurality of nano-volume channels, each nano-volume channel having at least one interior surface in communication with the at least one exterior surface that is selectively coated with an optionally dissolvable coating agent physisorbed to at least one interior surface, wherein the optionally dissolvable coating agent comprises a coating agent and a first component for the plurality of specified reactions. Methods for preparing and using such devices are also provided, as well as a method of registering a location of a dispenser array in relation to a microfluidic array. A first one of the dispenser array and the microfluidic array is movable in relation to the frame, and the other of the first one of the dispenser array and the microfluidic array is fixed relative to the frame. Quantities related to a vector displacement from the alignment position to a fixed position on the one of the dispenser array and the microfluidic array is determined. The quantities thus determined are used to guide positioning of the dispenser array relative to the microfluidic array.

1 - 90 . (canceled)  
     
     
         91 . A method for differentially coating a substrate having at least one exterior surface and a plurality of channels for liquid disposed therein, each channel having at least one interior surface in communication with at least one exterior surface, the method comprising: 
 applying a first coating agent to the substrate to create a coated substrate;    selectively modifying at least one exterior surface or at least one interior surface of the coated substrate with a first modifying agent to create at least one modified surface having a first specified physicochemical property and a non-modified surface such that the modified surface differs from the non-modified surface with respect to the first specified physicochemical property.    
     
     
         92 . A method according to  claim 91 , the method further comprising: 
 applying a second modifying agent to the at least one modified surface such that the second modifying agent imparts a second specified physicochemical property to the at least one modified surface.    
     
     
         93 . A method according to  claim 91 , the method further comprising: 
 applying the first modifying agent in a mixture of two or more modifying agents having distinct specified physicochemical properties to the at least one modified surface to create at least one modified surface having a mixture of distinct specified physicochemical properties.    
     
     
         94 . A method according to  claim 93 , wherein the at least one modified surface is a modified gradient surface having a gradient mixture of the distinct specified physicochemical properties.  
     
     
         95 . A method according to  claim 93 , wherein the at least one modified surface is a modified mixed-layer surface having a heterogeneous mixture of the distinct specified physicochemical properties.  
     
     
         96 . A method according to  claim 92 , the method further comprising: applying a third or more modifying agent to the at least one modified surface such that the third or more modifying agent imparts a third or more specified physicochemical property to the at least one modified surface.  
     
     
         97 . A method according to  claim 96  wherein the at least one modified surface has one or more of the first, second and third specified physicochemical properties.  
     
     
         98 - 101 . (canceled)  
     
     
         102 . A method according of claims  91  wherein the modifying agent is applied uniformly to create at least one uniformly modified surface.  
     
     
         103 . A method according of claims  91  wherein the modifying agent is applied non-uniformly to create at least one non-uniformly modified surface.  
     
     
         104 . A method according to  claim 103 , wherein the non-uniformly modified surface is non-uniform with respect to a property selected from the group consisting of concentration of modification, thickness of modification, continuity of modification, presence of the specified physicochemical property, and nature of the specified physicochemical property.  
     
     
         105 . A method according to  claim 91 , wherein selectively modifying further comprises: 
 selectively activating at least one interior surface or at least one exterior surface with an activating agent prior to selectively modifying said surface so as to create at least one activated surface; and    modifying the at least one activated surface by reacting said surface with the modifying agent to create at least one modified surface such that the at least one modified surface has the first specified physicochemical property.    
     
     
         106 - 107 . (canceled)  
     
     
         108 . A method according to  claim 91 , the method further comprising: 
 causing a blocking agent to adhere to at least one interior surface or at least one exterior surface prior to selectively applying the first coating agent so as to create at least one blocked surface; and    removing the blocking agent from the at least one blocked surface after applying the first coating agent.    
     
     
         109 - 113 . (canceled)  
     
     
         114 . A method according to  claim 91 , wherein the channels are selected from the group consisting of through-holes, passages and troughs  
     
     
         115 . A method according to of  claim 91 , wherein one or more of the first coating agent, first modifying agent, adheres to at least one exterior surface or at least one interior surface via physical interactions.  
     
     
         116 . (canceled)  
     
     
         117 . A method according to of  claim 91 , wherein one or more of the first coating agent, first modifying agent, adheres to at least one exterior surface or at least one interior surface via chemical bonding.  
     
     
         118 . (canceled)  
     
     
         119 . A method according to  claim 108 , wherein the first, modifying agent, first coating agent or blocking agent is selected from the group consisting of a polymer, a monomer, a cross-linking agent, a photo-cleavable agent, a silane, a lipid, a fatty acid, an amino acid, a peptide, a protein, an antibody, an enzyme, a surfactant, a micelle, a liposome, a nucleotide, an oligonucleotide, a nucleic acid, a salt, a wax, a low-melting solid, and an oil.  
     
     
         120 . (canceled)  
     
     
         121 . A method according to  claim 91 , wherein selectively modifying further comprises: 
 applying a solvent having a lower surface energy than that of the modifying agent to the at least one exterior surface or the at least one interior surface prior to applying the modifying agent.    
     
     
         122 . A method according to  claim 91 , wherein selectively modifying further comprises: 
 applying the modifying agent by subjecting the substrate to a pressure differential prior to applying the modifying agent.    
     
     
         123 . A method according to  claim 91 , wherein selectively modifying further comprises: 
 applying the modifying agent by subjecting the substrate to a liquid stream of modifying agent such that momentum from the liquid stream applies the modifying agent to the at least one interior surface.    
     
     
         124 . A method according to  claim 91 , wherein selectively modifying further comprises applying the modifying agent by exposing at least one exterior surface to a reactive vapor while subjecting at least one interior surface to a laminar flow stream of non-reactive gas such that the gas stream prevents the reactive vapor molecules from interacting with that interior surface.  
     
     
         125 - 127 . (canceled)  
     
     
         128 . A method according to  claim 108 , wherein the blocking agent makes at least one blocked surface one or more of impermeable to electrons; impermeable to ionizing radiation; or unavailable for or resistant to further chemical reaction, light-activated reaction, or chemical modification.  
     
     
         129 . (canceled)  
     
     
         130 . A method for differentially coating a substrate having at least one exterior surface and a plurality of channels for liquid disposed therein, each channel having at least one interior surface in communication with at least one exterior surface, the method comprising: 
 applying a first coating agent to the substrate to create a coated substrate; blocking at least one exterior surface or at least one interior surface of the coated substrate to create at least one blocked surface and at least one non-blocked surface;    selectively modifying the non-blocked surface with a modifying agent to create at least one modified surface and at least one non-modified surface such that the modified surface differs from the non-modified surface with respect to a specified physicochemical property; and    unblocking the at least one blocked surface.    
     
     
         131 - 132 . (canceled)  
     
     
         133 . A method according to  claim 130 , wherein selectively modifying comprises exposing the at least one non-blocked surface to UV radiation, ionizing radiation, an ion-beam, an electron beam, microwave radiation, visible light, a coherent light source, or a laser such that the specified physicochemical property is achieved  
     
     
         134 . A method according to  claim 130 , wherein selectively modifying comprises treating the at least one non-blocked surface with an etching material that removes the coating material from the non-blocked surface.  
     
     
         135 . A method according to  claim 91  wherein applying the first coating agent comprises uniformly or non-uniformly applying the coating agent.  
     
     
         136 . (canceled)  
     
     
         140 . A method according of  claim 91  wherein the specified physicochemical property of the at least one modified surface is a hydrophobic property or a hydrophilic property.  
     
     
         141 . A method according to  claim 108  wherein applying the first coating agent comprises uniformly or non-uniformly applying the coating agent.  
     
     
         142 - 143 . (canceled)  
     
     
         144 . A differentially coated device for conducting a plurality of nano-volume specified reactions, the device comprising: 
 a platen having at least one exterior surface modified to a specified physicochemical property;    a plurality of nano-volume channels, each nano-volume channel having at least one interior surface in communication with the at least one exterior surface;    wherein the at least one interior surface of one or more of the of nano-volume channels is selectively coated with a dissolvable coating agent physisorbed to the at least one interior surface, wherein the dissolvable coating agent comprises a coating agent and a first component for the plurality of specified reactions.    
     
     
         145 . A differentially coated device according to  claim 144 , wherein the coating agent is selected from the group consisting of a low melting-point solid; a hydratable solid, semi-solid or gel; a polymer; a block co-polymer; a polyethylene glycol; a polyvinyl alcohol; a lipid; a surfactant; a controlled-release agent; and a salt  
     
     
         146 . A method for preparing a differentially coated device according to  claim 144  for conducting a plurality of nano-volume specified reactions, the method comprising: 
 providing a device having a plurality of nano-volume channels for retaining one or more reaction components for the specified reactions, each nano-volume channel having at least one interior surface in communication with at least one exterior surface,    selectively coating at least one interior surface of one or more of the plurality of nano-volume channels with a dissolvable coating agent so as to prepare the differentially coated device, wherein the dissolvable coating agent is physisorbed to the at least one interior surface and comprises a coating agent and a first component for the plurality of specified reactions.    
     
     
         147 . A method for preparing a differentially coated device according to  claim 91 , wherein providing further comprises selectively coating at least one external surface with a coating agent to impart a specified physicochemical property using an autoloader device comprising a loading chamber sufficiently large to contain the device to be coated, the coating reagent, and an immiscible fluid that lifts the coating reagent over the device as the volume of the immiscible fluid is increased.  
     
     
         148 . (canceled)  
     
     
         149 . A method for conducting a plurality of nano-volume specified reactions according to  claim 146 , wherein loading further comprises using a pin-loading device comprising an array of calibrated transfer pin dispensers to load the plurality of channels with one or more reaction mixtures.  
     
     
         150 . A method for conducting a plurality of nano-volume specified reactions using the differentially coated device of  claim 144 , the method comprising: 
 loading the plurality of channels in the differentially coated device with one or more reaction mixtures comprising additional components sufficient for the plurality of specified reactions;    initiating the plurality of reactions by one or more methods selected from the group consisting of heating the device, exposing the device to photo/optical conditions, hydrating the nano-volume channels; and stacking the device with one or more other devices to mix components in each device upon contact, thus initiating the specified reactions.    
     
     
         151 . A method for conducting a plurality of nano-volume specified reactions according to  claim 150 , wherein loading further comprises using a pin-loading device comprising an array of calibrated transfer pin dispensers to load the plurality of nano-volume channels with one or more reaction mixtures.  
     
     
         152 . A method according to  claim 150 , wherein the plurality of channels may vary from channel to channel with respect to any or all of: 
 a specified reaction;    a sample;    a specified physicochemical property of the nano-volume channel; and    method of initiating a specified reaction.    
     
     
         153 - 156 . (canceled)  
     
     
         157 . A method according to  claim 150 , wherein the plurality of specified reactions comprise maintenance of cell cultures.  
     
     
         158 . A method for preparing a differentially coated device for conducting a plurality of nano-volume specified reactions, the method comprising: 
 providing a device having a plurality of channels for retaining one or more reaction components for the specified reactions, each channel having at least one interior surface in communication with at least one exterior surface,    selectively coating the at least one interior surface of one or more of the plurality of channels with a dissolvable coating agent so as to prepare the differentially coated device,    wherein the dissolvable coating agent is physisorbed to the at least one interior surface and comprises a coating agent and a first component for the plurality of specified reactions.    
     
     
         159 . A method for preparing a differentially coated device according to  claim 158 , wherein selectively coating further comprises using a pin-loading device comprising an array of calibrated transfer pin dispensers to selectively physisorb the dissolvable coating agent to the at least one interior surface.  
     
     
         160 . A method for conducting a plurality of nano-volume specified reactions using a first and at least second differentially coated device prepared according to  claim 159 , the method comprising: 
 loading the plurality of channels in the first differentially coated device with one or more samples, wherein the samples are the same or different;    initiating the plurality of reactions by stacking the first device with at least a second differentially coated device loaded with a mixture of reagents comprising sufficient components common to the specified reactions, such that upon stacking, the mixture of reagents in the at least second device mixes with the samples of the first device, thereby initiating the specified reactions.    
     
     
         161 . (canceled)  
     
     
         162 . A method for preparing a differentially coated device for conducting a plurality of nano-volume specified reactions, the method comprising: 
 preparing a platen having a prescribed spatial arrangement of nano-volume channels, each nano-volume channel having at least one interior surface in communication with at least one exterior surface,    wherein preparing further comprises:    coating a flexible printing pad with a coating agent;    transferring the coating on the flexible printing pad to the platen by contacting at least one external surface of the platen with the printing pad to impart the coating to the platen;    selectively coating the at least one interior surface of one or more of the plurality of nano-volume channels with a coating agent so as to prepare the differentially coated device, wherein the coating agent is physisorbed to the at least one interior surface and comprises a coating agent and optionally a first component for the plurality of specified reactions.