US2010301398A1PendingUtilityA1

Methods and apparatus for measuring analytes

65
Assignee: ION TORRENT SYSTEMS INCPriority: May 29, 2009Filed: May 29, 2009Published: Dec 2, 2010
Est. expiryMay 29, 2029(~2.8 yrs left)· nominal 20-yr term from priority
Inventors:Jonathan M. RothbergJames BustilloMark MilgrewJonathan SchultzDavid MarranTodd RearickKim L. Johnson
G01N 27/27G01N 27/414C12Q 1/6874G01N 27/4145Y10T29/49002C12Q 1/6869G01N 27/4148G01N 33/54373
65
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Claims

Abstract

Methods and apparatus relating to FET arrays including large FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.

Claims

exact text as granted — not AI-modified
1 . An apparatus, comprising:
 an array of sensors, each sensor comprising one chemically-sensitive field effect transistor (chemFET), said chemFET having a floating gate structure;   a layer of first material disposed over the sensor array and having formed therein a plurality of microwells, each microwell forming a cavity disposed over at least one of the chemFETS for receiving fluid analyte therein; and   a layer of protection material on said floating gate structure to separate the material of the floating gate from the analyte,   wherein the layer of protection material has a thickness over the floating gate structure of up to about 600 Angstroms.   
     
     
         2 . The apparatus of  claim 1 , wherein the layer of protection material has a thickness over the floating gate of up to about 400 Angstroms. 
     
     
         3 . The apparatus of  claim 1 , wherein the chemFETs are CMOS devices, and the protective layer of material comprises one or more layers of a CMOS passivation material. 
     
     
         4 . The apparatus of  claim 3 , wherein at least one layer of said passivation material is a metal oxide or metal nitride. 
     
     
         5 . The apparatus of  claim 4 , wherein the metal oxide or metal nitride is selected from among the group consisting of Al 2 O 3 , SiO 2 , Si 3 N 4 , Al 2 O 3 , Ta 2 O 5 , HfO 3 , WO 3 , and a super-Nernstian material. 
     
     
         6 . (canceled) 
     
     
         7 . The apparatus of  claim 1 , wherein the layer of first material and the layer of protection material comprise a single layer of material which has a thickness in areas not over the floating gate structures sufficient to form the microwells over the floating gate structures. 
     
     
         8 . The apparatus of  claim 7 , wherein the chemFETs are CMOS devices and the single layer of material comprises a CMOS process passivation material which is up to about 600 Angstroms thick over the floating gate structure and forms microwells at least about 1 μm deep. 
     
     
         9 . The apparatus of  claim 1 , wherein the protection layer also covers the sidewalls of the microwells. 
     
     
         10 . The apparatus of  claim 9 , wherein the protection layer has a pKa value that is closer to the analyte pH conditions than is the pKa value of the first material. 
     
     
         11 . (canceled) 
     
     
         12 . A method of forming an array of chemically-sensitive field effect transistors (chemFETs), each said chemFET having a floating gate structure, with a corresponding array of microwells disposed over the floating gate structures, each microwell forming a cavity disposed over the floating gate structure of at least one of the chemFETs for receiving fluid analyte therein, said method comprising:
 a. providing an array of chemFETs in a semiconductor substrate, the floating gate structures of the chemFETs being covered by a layer of protection material;   b. depositing a layer of material over the protection material and removing portions of said material over the floating gate structures to form said microwells therein; and   c. removing, if necessary, a portion of said layer of protection material so that a thickness of protection material of no more than about 600 Angstroms remains.   
     
     
         13 . The method of  claim 12 , wherein the chemFETs are CMOS devices, and the layer of protection material comprises one or more layers of a CMOS passivation material. 
     
     
         14 . The method of  claim 13 , wherein at least one layer of said passivation material is a metal oxide or metal nitride. 
     
     
         15 . The method of  claim 14 , wherein the metal oxide or metal nitride is selected from among the group consisting of Al 2 O 3 , SiO 2 , Si 3 N 4 , Al 2 O 3 , Ta 2 O 5 , HfO 3 , WO 3 , and a super-Nernstian material. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 12 , wherein the layer of first material and the layer of protection material comprise a single layer of material which has a thickness in areas not over the floating gate structures sufficient to form the microwells over the floating gate structures. 
     
     
         18 . The method of  claim 17 , wherein the chemFETs are CMOS devices and the single layer of material comprises a CMOS process passivation material which is up to about 600 Angstroms thick over the floating gate structure and forms microwells at least about 1 μm deep. 
     
     
         19 . A method of forming an array of chemically-sensitive field effect transistors (chemFETs), each said chemFET having a floating gate structure, with a corresponding array of microwells disposed over the floating gate structures, each microwell forming a cavity disposed over the floating gate structure of at least one of the chemFETs for receiving fluid analyte therein, said method comprising:
 a. providing an array of chemFETs in a semiconductor substrate, the floating gate structures of the chemFETs being covered by a layer of protection material;   b. substantially completely removing the protection material over the floating gate structures to form cavities in the protection material over the floating gate structures; and   c. depositing on the floating gate structures and sidewalls of said cavities a thin layer of a relatively high dielectric constant material and to a thickness of no more than about 600 Angstroms.   
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 19 , wherein the high dielectric constant material is a metal oxide or metal nitride. 
     
     
         22 . The method of  claim 19 , wherein the metal oxide or metal nitride is selected from among the group consisting of Al 2 O 3 , SiO 2 , Si 3 N 4 , Al 2 O 3 , Ta 2 O 5 , HfO 3 , WO 3 , and a super-Nernstian material. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 19  wherein depositing a thin layer of relatively high dielectric constant material further comprises depositing alternating layers of two materials, a first material exhibiting superior adhesion to the cavity walls than a second material which has a pKa value that is closer to the analyte pH conditions than is the pKa value of the first material. 
     
     
         25 . The method of  claim 24 , wherein the first material is Al 2 O 3  and the second material is Ta 2 O 5  and each of the alternating layers is about 10-20 Angstroms thick to a total thickness of up to about 600 Angstroms. 
     
     
         26 . The method of  claim 19  wherein depositing a thin layer of relatively high dielectric constant material further comprises depositing a first, very thin, layer of a material which adheres well to the walls of the cavities and a second, thicker layer of another material which has a pKa value that is close to the analyte pH conditions. 
     
     
         27 . (canceled)

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