Electrically active combinatorial chemical (eacc) chip for biochemical analyte detection

Abstract

Apparatus and methods are disclosed for electrically active combinatorial-chemical (EACC) chips for biochemical analyte detection. An apparatus includes a substrate that has an array of regions defining multiple cells, wherein each of the cells includes a reaction cavity that contains multiple functional binding groups. A method of detecting an analyte providing the reaction cavity between a source and a drain or a pair of electrodes, applying a voltage and monitoring a parameter indicative of an analyte characteristic. A process of fabricating an EACC include bonding an analyte to the multiple functional binding groups of each reaction cavity, and forming an analyte sensing structure including the substrate.

1 . An apparatus, comprising a substrate including an array of regions defining a plurality of cells, each of the plurality of cells including a reaction cavity containing multiple functional binding groups, wherein the array of regions comprises a first gradient of a first functional binding group and a second gradient of a second functional binding group, wherein a distance between the first functional binding group and the second functional binding group corresponds to an inter-molecular distance between binding locations on a biochemical analyte. 
     
     
         2 . The apparatus of  claim 1 , wherein the multiple functional binding groups are coupled to the substrate via hybridized DNA. 
     
     
         3 . The apparatus of  claim 1 , wherein the multiple functional binding groups are coupled to the substrate via a cross-linked polymer. 
     
     
         4 . The apparatus of  claim 1 , wherein the multiple functional binding groups are coupled to the substrate via a copolymer or chain transfer polymer or a combination thereof. 
     
     
         5 . The apparatus of  claim 1 , wherein the multiple functional binding groups are coupled to the substrate via a thiol-based reaction product. 
     
     
         6 . The apparatus of  claim 1 , wherein the plurality of cells each comprise an electrical sensing circuit. 
     
     
         7 . The apparatus of  claim 1 , wherein the plurality of cells each comprise an optical sensing structure. 
     
     
         8 . The apparatus of  claim 1 , wherein the plurality of cells comprise a protein chip having a feature size between 0.5 microns and 500 microns. 
     
     
         9 . The apparatus of  claim 8 , wherein the plurality of cells comprise a protein chip having a feature size of less than approximately 100 microns. 
     
     
         10 . The apparatus of  claim 8 , wherein the plurality of cells comprise a protein chip having a feature size of less than approximately one micron. 
     
     
         11 . The apparatus of  claim 1 , wherein the plurality of cells each comprise an electrically-active, combinatorial-chemical (EACC) chip for biochemical analyte detection. 
     
     
         12 . The apparatus of  claim 11 , wherein said analyte detection comprises probe-less detection. 
     
     
         13 . The apparatus of  claim 11 , wherein said analyte detection comprises creation of a binding site with one or more of the multiple functional binding groups. 
     
     
         14 . The apparatus of  claim 13 , wherein the groups comprise non-polymeric components. 
     
     
         15 . The apparatus of  claim 1 , wherein the first gradient is in a first direction or in the opposite direction or a combination thereof. 
     
     
         16 . The apparatus of  claim 15 , wherein the second gradient is in a second direction or in the opposite direction or a combination thereof. 
     
     
         17 . The apparatus of  claim 16 , wherein the second direction is approximately orthogonal to the first direction. 
     
     
         18 . The apparatus of  claim 1 , wherein the substrate comprises silicon having a surface modified with silanes. 
     
     
         19 . The apparatus of  claim 18 , wherein the silanes comprise phenyl. 
     
     
         20 . The apparatus of  claim 1 , wherein the multiple groups comprise a positively-charged group and a negatively charged group. 
     
     
         21 . The apparatus of  claim 1 , wherein the multiple groups comprise a polar group and a nonpolar group. 
     
     
         22 . The apparatus of  claim 21 , wherein the multiple groups comprise a positively-charged group and a negatively charged group. 
     
     
         23 . An apparatus, comprising a substrate including an array of transistor sensors defining a plurality of cells including a reaction cavities containing binding groups on the gates of transistors, wherein the cells are configured for monitoring a parameter indicative of an analyte characteristic when a voltage is applied between the sources and drains of the transistors. 
     
     
         24 . The apparatus of  claim 23 , further comprising a channel defined by an analyte bonded to a self-assembled monolayer. 
     
     
         25 . The apparatus of  claim 23 , comprising different chemical structures disposed on the gates of the transistors and contacting a sample. 
     
     
         26 . The apparatus of  claim 25 , wherein a set of pre-determined chemical structures are associated with a set of transistors. 
     
     
         27 . The apparatus of  claim 26 , wherein the cells are configured such that binding patterns are translated into generated electrical signals when source-drain voltages are applied that differ depending on the different pre-determined chemical structures. 
     
     
         28 . The apparatus of  claim 27 , further comprising a processor-based analyzer for identifying analytes in the sample by analyzing patterns of electrical signals generated by the transistors with respect to the gate-associated chemical compositions. 
     
     
         29 . The apparatus of  claim 28 , further comprising a pre-built database of standard analytes, wherein the analyzer uses computer pattern recognition in the identification. 
     
     
         30 .- 50 . (canceled)