Methods and apparatus for detecting molecular interactions using fet arrays

Abstract

Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

What is claimed is: 
     
         1 .- 23 . (canceled) 
     
     
         24 . A method for detecting a target analyte in a sample comprising
 providing an apparatus comprising a field-effect transistor array comprising at least 10 5  sensors, each sensor including a field-effect transistor comprising a floating gate structure and a dielectric layer formed on top of the floating gate structure, and a molecular recognition site on the surface of the dielectric layer, the molecular recognition site including a recognition molecule having a specificity for the target analyte;   disposing a sample in proximity to or in contact with at least a portion of the sensor array, and   identifying interactions between the recognition molecule and the target analyte present in the sample by detecting changes in electrical output of at least one of the field-effect transistors of the field-effect transistor array.   
     
     
         25 . The method of  claim 24 , wherein the interaction between recognition molecule and the target analyte causes a change in the concentration of an ionic species in proximity to the field-effect transistor. 
     
     
         26 . The method of  claim 24 , wherein the field-effect transistor is a chemical field-effect transistor or an ion-sensitive field-effect transistor. 
     
     
         27 . The method of  claim 24 , wherein the recognition molecules are uniformly applied to the surface of the dielectric layer. 
     
     
         28 . The method of  claim 24 , wherein the recognition molecules are arranged to form an array of individual recognition elements across the surface of the dialectic layer. 
     
     
         29 . The method of  claim 24 , wherein the target analyte includes a charged particle. 
     
     
         30 . The method of  claim 24 , wherein the charge particle includes a metal ion. 
     
     
         31 . The method of  claim 24 , wherein the recognition molecule includes a catcher molecule. 
     
     
         32 . The method of  claim 24 , wherein the recognition molecule includes an elongated tether. 
     
     
         33 . A method for detecting a target analyte in a sample comprising
 providing an apparatus comprising a field-effect transistor array comprising a plurality of sensors formed in a substrate, the sensors comprising a field-effect transistor having a floating gate structure comprising conductors formed in a plurality of conductor layers and electrically coupled to one another, a dielectric layer formed on top of the floating gate structure, and a molecular recognition site on the surface of the dielectric layer, the apparatus further comprising signal lines for the sensors within at least one of the conductor layers, the molecular recognition site including a recognition molecule having a specificity for the target analyte;   disposing a sample in proximity to or in contact with at least a portion of the sensor array, and   identifying interactions between the recognition molecule and the target analyte present in the sample by detecting changes in electrical output of at least one of the field-effect transistors of the field-effect transistor array.   
     
     
         34 . The method of  claim 33 , wherein the interaction between recognition molecule and the target analyte causes a change in the concentration of an ionic species in proximity to the field-effect transistor. 
     
     
         35 . The method of  claim 33 , wherein the field-effect transistor is a chemical field-effect transistor or an ion-sensitive field-effect transistor. 
     
     
         36 . The method of  claim 33 , wherein the recognition molecules are uniformly applied to the surface of the dielectric layer. 
     
     
         37 . The method of  claim 33 , wherein the recognition molecules are arranged to for an array of individual recognition elements across the surface of the dialectic layer. 
     
     
         38 . The method of  claim 33 , wherein the target analyte includes a charged particle. 
     
     
         39 . The method of  claim 33 , wherein the charged particle includes a metal ion. 
     
     
         40 . The method of  claim 39 , wherein the metal ion includes a heavy metal ion. 
     
     
         41 . The method of  claim 39 , wherein the metal ion includes a potassium ion, a calcium ion, or a sodium ion. 
     
     
         42 . The method of  claim 33 , wherein the recognition molecule includes a catcher molecule. 
     
     
         43 . The method of  claim 33 , wherein the recognition molecule includes an elongated tether. 
     
     
         44 . The method of  claim 43 , wherein the elongated tether includes polyethylene glycol (PEG) or poly ethyl acrylate (PEA). 
     
     
         45 . The method of  claim 43 , wherein the elongated tether includes a conductive molecule. 
     
     
         46 . The method of  claim 45 , wherein conductive molecule includes a carbon nanotube.