Biosensors array and method for operating a biosensor array

• US 20050247559A1
• Filed: 12/21/2004
• Published: 11/10/2005
• Est. Priority Date: 06/24/2002
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Vetmedica GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Infineon Technologies AG
• Inventors: Holzapfl, Birgit, Thewes, Roland, Frey, Alexander, Paulus, Christian, Schienle, Meinrad, Hofmann, Franz
• Granted Patent: US 8,702,921 B2
• Time in Patent Office: Days
• US Class Current: 204/403.10
• CPC Class Codes: G01N 27/3276 being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68

Abstract

A biosensor array having a substrate, a plurality of biosensor zones arranged on the substrate, each of which has a first terminal and a second terminal, at least one drive line and at least one detection line, the at least one drive line being electrically insulated from the at least one detection line. In each case the first terminal of each biosensor zone is coupled to precisely one of the at least one drive line and the second terminal of each biosensor zone is coupled to precisely one of the at least one detection line, and at least one of the at least one drive line and at least one of the at least one detection line is coupled to at least two of the biosensor zones. The biosensor array also has a drive unit for providing an electrical drive signal, a detection unit for detecting an electrical detection signal resulting from the electrical drive signal, and a selection unit that couples the drive unit to the drive line of a biosensor zone to be selected and the detection unit to the detection line of the biosensor zone to be selected, whereby the biosensor zone is selected.

Claims

1-49. -49. (canceled)

50. A biosensor array comprising:

a substrate;

a plurality of biosensor zones arranged on the substrate, each of which has a first terminal and a second terminal;

at least one drive line and at least one detection line, the at least one drive line being electrically insulated from the at least one detection line;

wherein in each case the first terminal of each biosensor zone is coupled to precisely one of the at least one drive line and the second terminal of each biosensor zone is coupled to precisely one of the at least one detection line, and at least one of the at least one drive line and at least one of the at least one detection line is coupled to at least two of the biosensor zones;

a drive unit for providing an electrical drive signal;

a detection unit for detecting an electrical detection signal resulting from the electrical drive signal; and

a selection unit that couples the drive unit to the drive line of a biosensor zone to be selected and the detection unit to the detection line of the biosensor zone to be selected, whereby the biosensor zone is selected.

51. The biosensor array as claimed in claim 50, further comprising an evaluation unit that determines for the at least one selected biosensor zone on the basis of the drive signal and the detection signal whether sensor events have taken place at the at least one selected biosensor zone and/or the quantity in which sensor events have taken place at the at least one selected biosensor zone.

52. The biosensor array as claimed in claim 50, wherein at least one of the biosensor zones is an electrochemical biosensor zone or an impedance biosensor zone.

53. The biosensor array as claimed in claim 52, wherein at least one biosensor zone set up as an electrochemical biosensor zone is a redox recycling biosensor zone.

54. The biosensor array as claimed in claim 50, wherein at least one biosensor zone is an interdigital electrode biosensor zone.

55. The biosensor array as claimed in claim 50, wherein the biosensor zones are grouped to form a plurality of biosensor groups such that each biosensor group can optionally be operated separately from the other biosensor groups or jointly with at least a portion of the other biosensor groups.

56. The biosensor array as claimed in claim 50, wherein the substrate is a ceramic substrate, a semiconductor substrate, a glass substrate, or a plastic substrate.

57. The biosensor array as claimed in claim 50, wherein the electrical drive signal is a temporally variable electrical signal.

58. The biosensor array as claimed in claim 50, wherein

the drive signal is a temporally variable electrical voltage and the detection signal is a temporally variable electric current;

or

the drive signal is a temporally variable electric current and the detection signal is a temporally variable electrical voltage.

59. The biosensor array as claimed in claim 51, wherein the substrate has integrated therein,

an analog-to-digital converter circuit, which can convert an analog electrical signal into a digital signal and provide the digital signal to the evaluation unit;

and/or

an electrical supply unit, which can provide electrical voltage signals and/or electric current signals to the drive unit and/or to the selection unit; and

/or

a digital-to-analog converter circuit, which can convert a digital voltage signal and/or current signal of the supply unit into an analog signal and provide the analog signal to the drive unit and/or to the selection unit; and

/or

an input/output interface; and

/or

an amplifier unit for amplifying the electrical detection signal.

60. The biosensor array as claimed in claim 50, wherein the at least one drive line and the at least one detection line are at least partly formed in two different line planes in and/or on and/or below the substrate.

61. The biosensor array as claimed in claim 60, wherein the biosensor zones are formed in precisely one of the line planes.

62. The biosensor array as claimed in claim 60, wherein, in a first line section, in which the at least one drive line and the at least one detection line are free of a mutual crossover, the at least one drive line and the at least one detection line are formed such that they run in the same plane, and in which, in a second line section, in which the at least one drive line and the at least one detection line mutually cross one another, the at least one drive line and the at least one detection line are formed such that they run in different planes.

63. The biosensor array as claimed in claim 62, wherein the first line section of the at least one drive line and/or of the at least one detection line are coupled to the second line section of the at least one drive line and/or of the at least one detection line by means of at least one electrical contact-connection element arranged in a manner essentially running vertically with respect to the substrate.

64. The biosensor array as claimed in claim 60, wherein the at least one drive line and/or the at least one detection line is formed in a manner running on an underside of the substrate or beneath the substrate.

65. The biosensor array as claimed in claim 50, wherein the drive unit has a supply unit that is common to all the biosensor zones and can be used to apply the electrical drive signal to the at least one selected biosensor zone.

66. The biosensor array as claimed in claim 65, wherein the drive unit and/or the detection unit are set up such that an electrical reference signal can be applied to at least a portion of the nonselected biosensor zones.

67. The biosensor array as claimed in claim 55, wherein the drive unit has, for a respective group of biosensor zones, a supply unit that is associated with the respective group and can be used to apply the electrical drive signal to the biosensor zones of the associated group.

68. The biosensor array as claimed in claim 50, wherein the detection unit has a measuring unit that is common to all the biosensor zones and can be used to detect the electrical detection signal at precisely one selected biosensor zone.

69. The biosensor array as claimed in claim 55, wherein the detection unit has, for a respective group of biosensor zones, a measuring unit that is associated with the respective group, and each of the measuring units can be used to detect the electrical detection signal at precisely one selected biosensor zone of the associated group.

70. The biosensor array as claimed in claim 50, further comprising a potentiostat device that can be used to predefine a constant electrical potential for at least a portion of the biosensor zones.

71. The biosensor array as claimed in claim 70, wherein the potentiostat device has a reference electrode, a counterelectrode, and an operational amplifier, and wherein a first input of the operational amplifier is coupled to the reference electrode, a second input of the operational amplifier is coupled to a reference potential, and an output of the operational amplifier is coupled to the counterelectrode.

72. A method for operating a biosensor array having a substrate, a plurality of biosensor zones arranged on the substrate, each of which has a first terminal and a second terminal, at least one drive line and at least one detection line, the at least one drive line being electrically insulated from the at least one detection line, wherein in each case the first terminal of each biosensor zone is coupled to precisely one of the at least one drive line and the second terminal of each biosensor zone being coupled to precisely one of the at least one detection line, at least one of the at least one drive line and at least one of the at least one detection line is coupled to at least two of the biosensor zones, a drive unit for providing an electrical drive signal, a detection unit for detecting an electrical detection signal resulting from the electrical drive signal, and a selection unit that couples the drive unit to the drive line of a biosensor zone to be selected and the detection unit to the detection line of the biosensor zone to be selected, whereby the biosensor zone is selected, the method comprising the steps of:

coupling the drive unit to the drive line of a biosensor zone to be selected and coupling the detection unit to the detection line of the biosensor zone to be selected, whereby the biosensor zone is selected;

providing the drive line of the selected biosensor zone with an electrical drive signal; and

detecting an electrical detection signal of the selected biosensor zone that results from the electrical drive signal, on the detection line of the selected biosensor zone.

73. The method as claimed in claim 72, wherein, for the at least one selected biosensor zone on the basis of the drive signal and the detection signal, determining whether sensor events have taken place at the at least one selected biosensor zone and/or the quantity in which sensor events have taken place at the at least one selected biosensor zone.

74. A biosensor array, comprising:

a substrate;

a plurality of biosensor zones arranged on the substrate, each of which biosensor zones has a first terminal and a second terminal;

at least one first signal line and at least one second signal line, wherein the at least one first signal line is electrically insulated from the at least one second signal line;

wherein in each case the first terminal of each biosensor zone is coupled to precisely one of the at least one first signal line and the second terminal of each biosensor zone is coupled to precisely one of the at least one second signal line, and at least one of the at least one first signal line and at least one of the at least one second signal line is coupled to at least two of the biosensor zones;

a first drive unit for providing a first electrical drive signal and a second drive unit for providing a second electrical drive signal;

a first detection unit coupled to the first drive unit and/or a second detection unit coupled to the second drive unit, which detects or detect a first and/or second electrical detection signal of a selected biosensor zone that results from the first and the second electrical drive signal; and

a selection unit that couples the first drive unit to the first signal line of a biosensor zone to be selected and the second drive unit to the second signal line of the biosensor zone to be selected, whereby the biosensor zone is selected.

75. The biosensor array as claimed in claim 74, further comprising an evaluation unit that determines for the at least one selected biosensor zone on the basis of the first and/or the second detection signal whether sensor events have taken place at the at least one selected biosensor zone and/or the quantity in which sensor events have taken place at the at least one selected biosensor zone.

76. The biosensor array as claimed in claim 74, wherein at least one of the biosensor zones is an electrochemical biosensor zone.

77. The biosensor array as claimed in claim 76, wherein at least one of the biosensor zones is a redox recycling biosensor zone.

78. The biosensor array as claimed in claim 74, wherein at least one of the biosensor zones has a first and a second electrode, the first electrode being coupled to the first terminal and the second electrode being coupled to the second terminal of the at least one biosensor zone.

79. The biosensor array as claimed in claim 78, wherein the first and the second electrodes are interdigital electrodes.

80. The biosensor array as claimed in claim 74, wherein the biosensor zones are grouped to form a plurality of biosensor groups such that each biosensor group can optionally be operated separately from the other biosensor groups or jointly with at least a portion of the other biosensor groups.

81. The biosensor array as claimed in claim 74, wherein the substrate is a ceramic substrate, a semiconductor substrate, a glass substrate, or a plastic substrate.

82. The biosensor array as claimed in claim 74, wherein the first and the second electrical drive signals are electrical DC voltage signals having a different sign, and wherein the first and/or second electrical detection signal is an electric current.

83. The biosensor array as claimed in claim 74, wherein the values of the first and of the second electrical drive signals are set such that, on account of a sensor event that has taken place at a biosensor zone, a significant first and/or second detection signal is generated essentially only when the first terminal of the biosensor zone is coupled to the first drive unit and the second terminal of the biosensor zone is coupled to the second drive unit.

84. The biosensor array as claimed in claim 75, wherein, integrated in the substrate is,

an analog-to-digital converter circuit, which can convert an analog electrical signal into a digital signal and provide the digital signal to the evaluation unit;

and/or

an electrical supply unit, which can provide electrical voltage signals and/or electric current signals to the first and/or the second drive unit and/or to the selection unit; and

/or

a digital-to-analog converter circuit, which can convert a digital signal of the supply unit into an analog signal and provide the analog signal to the drive unit and/or to the selection unit; and

/or

an input/output interface; and

/or

an amplifier unit for amplifying the first and/or the second electrical detection signal.

85. The biosensor array as claimed in claim 74, wherein the at least one first signal line and the at least one second signal line are at least partly formed in two different line planes in and/or on and/or below the substrate.

86. The biosensor array as claimed in claim 85, wherein the biosensor zones are formed in precisely one of the line planes.

87. The biosensor array as claimed in claim 85, wherein, in a first line section, in which the at least one first signal line and the at least one second signal line are free of a mutual crossover, the at least one first signal line and the at least one second signal line are formed such that they run in the same plane, and in which, in a second line section, in which the at least one first signal line and the at least one second signal line mutually cross one another, the at least one first signal line and the at least one second signal line are formed such that they run in different planes.

88. The biosensor array as claimed in claim 87, wherein the first line section of the at least one first signal line and/or of the at least one second signal line are coupled to the second line section of the at least one first signal line and/or of the at least one second signal line by means of at least one electrical contact-connection element arranged in a manner essentially running vertically with respect to the substrate.

89. The biosensor array as claimed in claim 85, wherein the at least one first signal line and/or the at least one second signal line is formed in a manner running on an underside of the substrate or beneath the substrate.

90. The biosensor array as claimed in claim 74, wherein the first drive unit has a first supply unit that is common to all the biosensor zones and/or the second drive unit has a second supply unit that is common to all the biosensor zones, wherein the first supply unit can be used to apply the first electrical drive signal to the at least one selected biosensor zone, and/or the second supply unit can be used to apply the second electrical drive signal to the at least one selected biosensor zone.

91. The biosensor array as claimed in claim 90, wherein the first and second drive units are set up such that an electrical reference signal can be applied to at least a portion of the nonselected biosensor zones, the value of said electrical reference signal essentially being the average value of the first and the second drive signals.

92. The biosensor array as claimed in claim 74, wherein the first drive unit has, for a respective first group of biosensor zones, a first supply unit that is associated with the respective group, which first supply unit can be used to apply the first electrical drive signal to the biosensor zones of the associated first group, and/or wherein the second drive unit has, for a respective second group of biosensor zones, a second supply unit that is associated with the respective group, which second supply unit can be used to apply the second electrical drive signal to the biosensor zones of the associated second group.

93. The biosensor array as claimed in claim 74, wherein the first detection unit has a first measuring unit that is common to all the biosensor zones, which first measuring unit can be used to detect the electrical first detection signal at precisely one selected biosensor zone, and/or wherein the second detection unit has a second measuring unit that is common to all the biosensor zones, which second measuring unit can be used to detect the electrical second detection signal at precisely one selected biosensor zone.

94. The biosensor array as claimed in claim 92, wherein the first detection unit has, for a respective third group of biosensor zones, a first measuring unit that is associated with the respective third group, wherein each of the first measuring units can be used to detect the electrical first detection signal at precisely one selected biosensor zone of the associated third group, and/or wherein the second detection unit has, for a respective fourth group of biosensor zones, a second measuring unit that is associated with the respective fourth group, wherein each of the second measuring units can be used to detect the electrical second detection signal at precisely one selected biosensor zone of the associated fourth group.

95. The biosensor array as claimed in claim 74, further comprising a potentiostat device that can be used to predefine a constant electrical potential for an electrolyte introduced into at least a portion of the biosensor zones.

96. The biosensor array as claimed in claim 95, wherein the potentiostat device has a reference electrode, a counterelectrode, and an operational amplifier, wherein a first input of the operational amplifier is coupled to the reference electrode, a second input of the operational amplifier is coupled to a reference potential, and an output of the operational amplifier is coupled to the counterelectrode.

97. A method for operating a biosensor array having a substrate, a plurality of biosensor zones arranged on the substrate, each of which has a first terminal and a second terminal, at least one first signal line and at least one second signal line, the at least one first signal line being electrically insulated from the at least one second signal line, wherein in each case the first terminal of each biosensor zone is coupled to precisely one of the at least one first signal line and the second terminal of each biosensor zone is coupled to precisely one of the at least one second signal line, at least one of the at least one first signal line and at least one of the at least one second signal line is coupled to at least two of the biosensor zones, a first drive unit for providing a first electrical drive signal and a second drive unit for providing a second electrical drive signal, a first detection unit coupled to the first drive unit and/or having a second detection unit coupled to the second drive unit, which detects or detect a first and/or second electrical detection signal of a selected biosensor zone that results from the first and the second electrical drive signal, a selection unit that couples the first drive unit to the first signal line of a biosensor zone to be selected and the second drive unit to the second signal line of the biosensor zone to be selected, whereby the biosensor zone is selected, the method comprising the steps of:

coupling the first drive unit to the first signal line of a biosensor zone to be selected and coupling the second drive unit to the second signal line of the biosensor zone to be selected, whereby the biosensor zone is selected;

providing the first signal line of the selected biosensor zone with a first electrical drive signal and providing the second signal line of the selected biosensor zone with a second electrical drive signal; and

detecting a first detection signal resulting from the first and the second electrical drive signals on the first signal line of the selected biosensor zone and/or detecting a second detection signal resulting from the first and the second electrical drive signals on the second signal line of the selected biosensor zone.

98. The method as claimed in claim 97, wherein, for the at least one selected biosensor zone on the basis of the first and/or the second detection signal, determining whether sensor events have taken place at the at least one selected biosensor zone and/or the quantity in which sensor events have taken place at the at least one selected biosensor zone.

99. A biosensor array comprising:

a substrate;

a plurality of biosensor zones arranged on the substrate, each of which has a first terminal and a second terminal;

at least one drive line and at least one detection line, the at least one drive line being electrically insulated from the at least one detection line;

wherein in each case the first terminal of each biosensor zone is coupled to precisely one of the at least one drive line and the second terminal of each biosensor zone is coupled to precisely one of the at least one detection line, and at least one of the at least one drive line and at least one of the at least one detection line is coupled to at least two of the biosensor zones;

a drive means for providing an electrical drive signal;

a detection means for detecting an electrical detection signal resulting from the electrical drive signal; and

a selection means for coupling the drive means to the drive line of a biosensor zone to be selected and the detection means to the detection line of the biosensor zone to be selected, whereby the biosensor zone is selected.

100. The biosensor array as claimed in claim 99, further comprising:

means for providing the drive line of the selected biosensor zone with an electrical drive signal; and

means for detecting an electrical detection signal of the selected biosensor zone that results from the electrical drive signal, on the detection line of the selected biosensor zone.

101. A biosensor array, comprising:

a substrate;

a plurality of biosensor zones arranged on the substrate, each of which biosensor zones has a first terminal and a second terminal;

at least one first signal line and at least one second signal line, wherein the at least one first signal line is electrically insulated from the at least one second signal line;

wherein in each case the first terminal of each biosensor zone is coupled to precisely one of the at least one first signal line and the second terminal of each biosensor zone is coupled to precisely one of the at least one second signal line, and at least one of the at least one first signal line and at least one of the at least one second signal line is coupled to at least two of the biosensor zones;

a first drive means for providing a first electrical drive signal and a second drive means for providing a second electrical drive signal;

a first detection means coupled to the first drive means and/or a second detection means coupled to the second drive means, which detects or detect a first and/or second electrical detection signal of a selected biosensor zone that results from the first and the second electrical drive signal; and

a selection means that couples the first drive means to the first signal line of a biosensor zone to be selected and the second drive means to the second signal line of the biosensor zone to be selected, whereby the biosensor zone is selected.

102. The biosensor as claimed in claim 101, further comprising:

means for providing the first signal line of the selected biosensor zone with a first electrical drive signal and providing the second signal line of the selected biosensor zone with a second electrical drive signal; and

means for detecting a first detection signal resulting from the first and the second electrical drive signals on the first signal line of the selected biosensor zone and/or detecting a second detection signal resulting from the first and the second electrical drive signals on the second signal line of the selected biosensor zone.