Microfluidic System Having Monolithic Nanoplasmonic Structures

Abstract

A microfluidic system, particularly suited as a cell culture system, is provided having a single monolithic biocompatible substrate with both a surface having an ordered array of nano-scale elements required for plasmonic response monitoring and a network of microchannels for precisely controlling cellular environment. The system has the additional advantages of low-volume consumption, rapid low-cost fabrication of molds with easily interchangeable microfluidic channel layouts, amenability to mass production, and in situ label-free real-time detection of cellular response, viability, behavior and biomolecular binding using plasmonic techniques. A ratio of greater than 0.2 between the cross-sectional dimension and the spacing distance of the nano-scale elements is useful for plasmonic response monitoring. A process for producing such a system involves fabrication of a master mold containing the nano-scale elements etched into a hard substrate, and the micro-scale and meso-scale features, such as channels and chambers, provided in a soft membrane bonded to the hard substrate. A stamp may be created by setting a settable liquid polymer or metal placed in the master mold and then the features of the intended device transferred to a polymeric substrate using the stamp.

1 . A stamp for patterning a polymeric substrate, the stamp comprising:
 a stamp body formed of a polymer or metal of sufficient hardness to be able to pattern the polymeric substrate, the stamp body having a surface bearing a pattern of micro-scale and/or meso-scale reliefs for forming one or more channels and/or microfluidic chambers,   wherein:
 one or more of the micro-scale and/or meso-scale reliefs has a surface with one or more nano-scale relief patterns for forming one or more ordered arrays of nano-scale elements in the polymeric substrate; 
 the nano-scale elements have cross-sectional dimensions in a range of from 10 nm to 1000 nm; and 
 the arrays have a spacing distance between the elements where a cross-sectional dimension to spacing distance ratio is greater than 0.2. 
   
     
     
         2 . The stamp according to  claim 1 , wherein the polymer or metal of sufficient hardness comprises a photocured thermoset polymer. 
     
     
         3 . The stamp according to  claim 1 , wherein size, spacing, geometry or any combination thereof of the nano-scale relief patterns have standard deviations from their respective averages of no more than 3%. 
     
     
         4 . The stamp according to  claim 1 , wherein the cross-sectional dimension to spacing distance ratio is in a range of from 0.2 to 1.5. 
     
     
         5 . The stamp according to  claim 1 , wherein the cross-sectional dimension to spacing distance ratio is in a range of from 0.5 to 1. 
     
     
         6 . The stamp according to  claim 1 , wherein the nano-scale relief patterns are for forming one or more of nanopillars, nanoposts, nanodots, nanorods, nanopyramids, nanocrescents, nanodisks, nanodomes, nanoholes, nanogratings and nanogrooves in the polymeric substrate. 
     
     
         7 . The stamp according to  claim 1  wherein:
 the nano-scale relief patterns are patterned on microstructural reliefs to provide two levels of topographical cues in the polymeric substrate; 
 an aspect ratio of individual nano-scale reliefs is in a range of from 10:1 to 1:10; or 
 at least one nano-scale relief pattern is on a micro-scale and/or meso-scale relief for forming a microfluidic chamber. 
 
     
     
         8 . A method for forming a stamp for producing a patterned polymeric substrate, the method comprising:
 micro-patterning a polymeric film to form a membrane comprising a first surface bearing a pattern of micro-scale and/or meso-scale features for defining one or more channels and/or chambers, one or more of the micro-scale and/or meso-scale features comprising at least one through-hole;   patterning a hard substrate to provide one or more ordered patterns;   placing the membrane on the hard substrate with a surface opposite the first surface against the hard substrate, the at least one through-hole aligned to expose the one or more ordered patterns, and applying pressure sufficient to seal lips of the membrane surrounding the through-holes against the hard substrate; and   placing a settable liquid polymer or metal in the through-holes and over the first surface and setting the settable liquid polymer or metal to form a stamp, the stamp comprising micro- scale and/or meso-scale reliefs for defining one or more channels and/or microfluidic chambers and further comprising one or more nano-scale relief patterns on the micro-scale and/or meso- scale reliefs that complement the one or more ordered patterns.   
     
     
         9 . The process according to  claim 8 , wherein size, spacing, geometry or any combination thereof of the nano-scale elements in the ordered patterns have standard deviations from their respective averages of no more than 3%. 
     
     
         10 . The process according to  claim 8 , wherein the cross-sectional dimension to spacing distance ratio is in a range of from 0.2 to 1.5. 
     
     
         11 . The process according to  claim 8 , wherein the cross-sectional dimension to spacing distance ratio is in a range of from 0.5 to 1. 
     
     
         12 . The process according to  claim 8 , wherein:
 the hard substrate comprises a cyclo-olefin polymer;   the nano-scale elements comprise one or more of nanopillars, nanoposts, nanodots, nanorods, nanopyramids, nanocrescents, nanodisks, nanodomes, nanoholes, nanogratings and nanogrooves;   the polymeric film comprises a thermoplastic elastomer;   the micro-scale and/or meso-scale features further define one or more valves, conduits, inlets or outlets;   the nano-scale elements are patterned on microstructures to provide two levels of topographical cues; or   an aspect ratio of individual nano-scale elements is in a range of from 10:1 to 1:10.   
     
     
         13 . The process according to  claim 8 , wherein at least one additional membrane comprising a pattern of micro-scale and/or meso-scale features for defining one or more channels and/or chambers is stacked on the membrane placed on the hard substrate. 
     
     
         14 . The process according to  claim 8 , wherein the stamp is formed from a settable polymer, the settable polymer comprises a photocurable polymer and the photocurable polymer is cured by exposing the photocurable polymer to ultraviolet light. 
     
     
         15 . The process according to  claim 8 , wherein at least one ordered array of nano-scale elements is in a microfluidic chamber. 
     
     
         16 . A utilization of the stamp of  claim 1 , for forming a nanoplasmonic microfluidic device, the utilization comprising:
 stamping a polymeric substrate with the stamp to form in the polymeric substrate, the one or more channels and/or microfluidic chambers in the polymeric substrate, and one or more surfaces having one or more nano-scale elements determined by the one or more ordered patterns etched onto the hard substrate.   
     
     
         17 . The utilization of  claim 16  further comprising treating the nano-scale elements of the ordered array to enhance or alter its properties. 
     
     
         18 . The utilization of  claim 17  wherein treating the nanoscale elements comprises metallization of the nano-scale elements. 
     
     
         19 . The utilization of  claim 18  wherein metallization of the nano-scale elements are metallized with one or more of: silver, gold, copper, platinum and palladium by evaporation, sputtering or plating. 
     
     
         20 . The utilization of  claim 17  wherein treating the nanoscale elements comprises chemical surface modification of the nano-scale elements.