Methods and apparatus for measuring analytes using large scale FET arrays

• US 20090127589A1
• Filed: 12/14/2007
• Published: 05/21/2009
• Est. Priority Date: 12/14/2006
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: ION Torrent Systems Incorporated (Thermo Fisher Scientific Incorporated)
• Inventors: Rothberg, Jonathan M., Hinz, Wolfgang, Johnson, Kim L., Bustillo, James
• Granted Patent: US 7,948,015 B2
• Time in Patent Office: Days
• US Class Current: 257/253
• CPC Class Codes: C12Q 1/6818 involving interaction of two or more labels, e.g. resonant energy transfer
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2533/101 Primer extension
• CPC Class Codes: C12Q 2565/301 Pyrophosphate (PPi)
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 27/4148 Integrated circuits therefor, e.g. fabricated by CMOS processing CMOS processing per se H01L21/82
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: H01L 27/088 the components being field-effect transistors with insulated gate
• CPC Class Codes: H01L 29/42324 Gate electrodes for transistors with a floating gate
• CPC Class Codes: H01L 29/78 with field effect produced by an insulated gate H01L29/7725, H01L29/775, H01L29/778 take precedence
• CPC Class Codes: H01L 2924/01006 Carbon [C]
• CPC Class Codes: H01L 2924/01013 Aluminum [Al]
• CPC Class Codes: H01L 2924/01015 Phosphorus [P]
• CPC Class Codes: H01L 2924/01073 Tantalum [Ta]
• CPC Class Codes: H01L 2924/14 Integrated circuits
• CPC Class Codes: H01L 2924/1433 Application-specific integrated circuit [ASIC]
• CPC Class Codes: Y10T 436/22 Hydrogen, per se

Abstract

Methods and apparatus relating to very large scale FET arrays for analyte measurements. 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. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

Claims

1. An apparatus, comprising:

an array (100) of CMOS-fabricated sensors (105), each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150) and occupying an area on a surface of the array of approximately ten micrometers by ten micrometers or less.

2-20. -20. (canceled)

21. A sensor array (100), comprising:

a two-dimensional array of electronic sensors (105) including at least 512 rows and at least 512 columns of the electronic sensors, each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150) configured to provide at least one output signal representing a presence and/or concentration of an analyte proximate to a surface of the two-dimensional array.

22-40. -40. (canceled)

41. An apparatus, comprising:

an array (100) of CMOS-fabricated sensors (105), each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150),

wherein the array of CMOS-fabricated sensors includes more than 256 sensors, wherein a collection of chemFET output signals from all chemFETs of the array constitutes a frame of data, and wherein the apparatus further comprises;

control circuitry (110, 192, 194, 198) coupled to the array and configured to generate at least one array output signal (Vout) to provide multiple frames of data from the array at a frame rate of at least 1 frame per second.

42-50. -50. (canceled)

51. An apparatus, comprising:

an array (100) of CMOS-fabricated sensors (105), each sensor comprising a chemically-sensitive field effect transistor (chemFET) (150), the chemFET comprising;

a floating gate structure (170); and

a source (156) and a drain (158) having a first semiconductor type and fabricated in a region (154) having a second semiconductor type, wherein there is no electrical conductor that electrically connects the region having the second semiconductor type to either the source or the drain.

52-73. -73. (canceled)

74. An apparatus, comprising:

an array (100) of electronic sensors (105), each sensor consisting of three field effect transistors (FETs) including one chemically-sensitive field effect transistor (chemFET) (150).

75. (canceled)

76. An apparatus, comprising:

an array (100) of electronic sensors (105), each sensor comprising three or fewer field effect transistors (FETs), wherein the three or fewer FETs includes one chemically-sensitive field effect transistor (chemFET) (150).

77. An apparatus, comprising:

an array (100) of electronic sensors (105), each sensor comprising;

a plurality of field effect transistors (FETs) including one chemically-sensitive field effect transistor (chemFET) (150); and

a plurality of electrical conductors electrically connected to the plurality of FETs,

wherein the plurality of FETs are arranged such that the plurality of electrical conductors includes no more than four conductors traversing an area occupied by each sensor and interconnecting multiple sensors of the array.

78. An apparatus, comprising:

an array (100) of CMOS-fabricated sensors (105), each sensor comprising a plurality of field effect transistors (FETs) including one chemically-sensitive field effect transistor (chemFET) (150), wherein all of the FETs in each sensor are of a same channel type and implemented in a single semiconductor region of an array substrate.

79. (canceled)

80. A sensor array (100), comprising:

a plurality of electronic sensors (105) arranged in a plurality of rows and a plurality of columns, each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150) configured to provide at least one output signal representing a presence and/or a concentration of an analyte proximate to a surface of the array,

wherein for each column of the plurality of columns, the array further comprises;

column circuitry (110) configured to provide a constant drain current and a constant drain-to-source voltage to respective chemFETs in the column, the column circuitry including two operational amplifiers and a diode-connected FET arranged in a Kelvin bridge configuration with the respective chemFETs to provide the constant drain-to-source voltage.

81. A sensor array (100), comprising:

a plurality of electronic sensors (105) arranged in a plurality of rows and a plurality of columns, each sensor comprising one chemically-sensitive field effect transistor (chemFET) (150) configured to provide at least one output signal representing a concentration of ions in an analyte proximate to a surface of the array;

at least one row select shift register (192) to enable respective rows of the plurality of rows; and

at least one column select shift register (194) to acquire chemFET output signals from respective columns of the plurality of columns.

82-85. -85. (canceled)

86. An apparatus, comprising:

an array (100) of CMOS-fabricated sensors (105), each sensor comprising a chemically-sensitive field effect transistor (chemFET) (150), the chemFET comprising;

a floating gate structure (170); and

a source (156) and a drain (158) having a first semiconductor type and fabricated in a region (154) having a second semiconductor type, wherein there is no electrical conductor that electrically connects the region having the second semiconductor type to either the source or the drain,

wherein;

the array includes a two-dimensional array of at least 512 rows and at least 512 columns of the CMOS-fabricated sensors;

each sensor consists of three field effect transistors (FETs) including the chemFET;

each sensor includes a plurality of electrical conductors electrically connected to the three FETs;

the three FETs are arranged such that the plurality of electrical conductors includes no more than four conductors traversing an area occupied by each sensor and interconnecting multiple sensors of the array;

all of the FETs in each sensor are of a same channel type and implemented in a single semiconductor region of an array substrate; and

a collection of chemFET output signals from all chemFETs of the array constitutes a frame of data,

and wherein the apparatus further comprises;

control circuitry (110, 192, 194, 198) coupled to the array and configured to generate at least one array output signal (Vout) to provide multiple frames of data from the array at a frame rate of at least 20 frames per second.

87. A method for processing an array (100) of CMOS-fabricated sensors (105), each sensor comprising a chemically-sensitive field effect transistor (chemFET) (150), the method comprising:

A) dicing a semiconductor wafer including the array to form at least one diced portion including the array; and

B) performing a forming gas anneal on the at least one diced portion.

88-93. -93. (canceled)

94. A method for processing an array (100) of CMOS-fabricated sensors (105), each sensor comprising a chemically-sensitive field effect transistor (chemFET) (150) having a chemically-sensitive passivation layer of silicon nitride and/or silicon oxynitride deposited via plasma enhanced chemical vapor deposition (PECVD), the method comprising:

A) depositing at least one additional passivation material on the chemically-sensitive passivation layer so as to reduce a porosity and/or increase a density of the passivation layer.

95-101. -101. (canceled)

102. An apparatus comprising

a chemical-sensitive field effect transistor (chemFET) having disposed on its surface a PPi receptor.

103. A fluidics assembly for use with an array of sensors on an active semiconductor device capped with a protective layer, comprising:

a first member having therein an aperture for mating to the sensor array; and

a second member fixed to the first member in a fluid-tight seal therebetween, and having first and second fluid ports for supporting fluid passage, the first and second members and the sensor array defining a fluid chamber,

whereby fluid introduced into one of said ports flows over the array before exiting via the other of said ports.

104. A fluidics assembly for use with an array of sensors on an active semiconductor device capped with a protective layer, comprising:

a microwell array configured and arranged to provide fluid access to said protective layer;

a first member having therein an aperture for mating to the sensor array around the microwell array; and

a second member fixed to the first member in a fluid-tight seal therebetween, and having first and second fluid ports for supporting fluid passage, the first and second members and the microwell array defining a fluid chamber over the protective layer of the semiconductor device when mated to the sensor array,

whereby fluid introduced into one of said ports flows over the microwell array before exiting via the other of said ports and the active semiconductor device senses chemical activity in at least some of the microwells in the microwell array.

105-106. -106. (canceled)