SUBSYSTEMS AND METHODS FOR USE IN PATCH CLAMP SYSTEMS

• US 20090085584A1
• Filed: 12/04/2008
• Published: 04/02/2009
• Est. Priority Date: 05/04/2007
• Status: Active Grant

• Current Assignee: Tecella LLC
• Original Assignee: Tecella LLC
• Inventors: Tanaka, Yokichi J.
• Granted Patent: US 7,741,829 B2
• Time in Patent Office: Days
• US Class Current: 324/677
• CPC Class Codes: G01N 33/48728 Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10

Abstract

Subsystems and methods for use in patch clamp systems are provided. For example, in certain embodiments, compensation circuitry is used to compensate for non-idealities present in the patch clamp system. The accuracy of this compensation may be verified by employing, for example, circuitry that models the patch clamp system.

Claims

1-52. -52. (canceled)

53. A method for determining a capacitance of a device used to hold a cell in an electrophysiological experiment, the method comprising:

applying a stimulus to the device through a force amplifier;

measuring a response to the stimulus with a separate sense amplifier; and

determining the capacitance of the device by analyzing the response to the stimulus.

54. The method of claim 53 further comprising employing compensation circuitry to compensate for the capacitance of the device.

55. The method of claim 53, wherein determining the capacitance of the device comprises calculating an RC time constant of the response to the stimulus.

56. A subsystem for determining a capacitance of a device used to hold a cell in an electrophysiological experiment, the subsystem comprising:

a force amplifier configured to apply a stimulus to the device;

a separate sense amplifier configured to measure a response to the stimulus; and

a determination module configured to determine the capacitance of the device by analyzing the response to the stimulus.

57. The subsystem of claim 56 further comprising compensation circuitry configured to compensate for the capacitance of the device.

58. The subsystem of claim 56, wherein the determination module is configured to calculate an RC time constant of the response to the stimulus in determining the capacitance of the device.

59-67. -67. (canceled)

68. A method of compensating for a capacitive waveform present in a patch clamp system, comprising:

measuring a magnitude of the capacitive waveform at each of a plurality of times; and

outputting a gain-adjusted compensatory waveform from each of a plurality of compensation circuits to compensate for the capacitive waveform,

wherein each compensation circuit has a unique time constant.

69. The method of claim 68 further comprising outputting an unadjusted compensatory waveform from each of the plurality of compensation circuits.

70. The method of claim 69 further comprising measuring a magnitude of each unadjusted compensatory waveform at each of the plurality of times.

71. The method of claim 70 further comprising calculating a gain adjustment for each of the plurality of compensation circuits.

72. The method of claim 71, wherein each gain adjustment is calculated based on the measured magnitude of the capacitive waveform at each of the plurality of times and the measured magnitude of each unadjusted compensatory waveform at each of the plurality of times.

73. The method of claim 68 further comprising calculating a leakage resistance present in the patch clamp system.

74. The method of claim 73 further comprising adjusting the measurement of the capacitive waveform to account for a virtual peak to be introduced into the capacitive waveform following compensation of the leakage resistance.

75. The method of claim 73 further comprising compensating for the leakage resistance present in the patch clamp system.

76. The method of claim 75 further comprising re-measuring the magnitude of the capacitive waveform at each of the plurality of times while the leakage resistance is compensated for.

77. A subsystem for compensating for a capacitive waveform present in a patch clamp system, comprising:

measurement circuitry for measuring a magnitude of the capacitive waveform at each of a plurality of times; and

a plurality of compensation circuits, each compensation circuit having a unique time constant and configured to output a gain-adjusted compensatory waveform to compensate for the capacitive waveform.

78. The subsystem of claim 77, wherein each compensation circuit is further configured to output an unadjusted compensatory waveform.

79. The subsystem of claim 78, wherein the measurement circuitry is further configured to measure a magnitude of each unadjusted compensatory waveform at each of the plurality of times.

80. The subsystem of claim 79 further comprising calculation circuitry for calculating a gain adjustment for each of the plurality of compensation circuits.

81. The subsystem of claim 80, wherein each gain adjustment is calculated based on the measured magnitude of the capacitive waveform at each of the plurality of times and the measured magnitude of each unadjusted compensatory waveform at each of the plurality of times.

82. The subsystem of claim 77 further comprising calculation circuitry for calculating a leakage resistance present in the patch clamp system.

83. The subsystem of claim 82, wherein the calculation circuitry is further configured to adjust the measurement of the capacitive waveform to account for a virtual peak to be introduced into the capacitive waveform following compensation of the leakage resistance.

84. The subsystem of claim 82 further comprising leakage resistance compensation circuitry for compensating the leakage resistance present in the patch clamp system.

85. The subsystem of claim 84, wherein the measurement circuitry is further configured to re-measure the magnitude of the capacitive waveform at each of the plurality of times while the leakage resistance compensation circuitry compensates the leakage resistance.