Process and apparatus for measuring binding events on a microarray of electrodes
First Claim
1. A process for reading electrical current of electrodes on a microarray of electrodes comprising the steps of:
- (a) providing a measurement system having a control system, an integration circuit, a microarray chamber, a plurality of voltage lines, an analog to digital converter connected to digital circuitry and analog circuitry, where the analog circuitry includes the integration circuit, where the digital circuitry is separate from the analog circuitry and includes the control system, where the control system, the integration circuit, and the microarray chamber are in circuit communication, where the microarray chamber contains a microarray having a plurality of electrodes in circuit communication with the control system and the integration circuit, where the voltage lines are switchably connectable to each electrode by the control system, where the integration circuit has a capacitance value, where the integration circuit has an integrating transimpedance amplifier having a positive input and a potentiometer circuit connected to the positive input via an operational amplifier;
(b) initializing measurement by setting a measurement set of the electrodes to approximately ground, setting a counter electrode voltage of at least one counter electrode, and pausing for a steady state period, where the at least one counter electrode is in fluid communication with the measurement set of the electrodes;
(c) measuring the current for each electrode of the measurement set of electrodes by (i) using a first voltage line to connect a measurement electrode to the integration circuit, the integration circuit having a reset switch, where the reset switch is in the closed position, (ii) pausing for an electrode settling period, (iii) opening the reset switch to measure and record a voltage response from the output of the integration circuit for a measurement time at a sampling rate, (iv) closing the reset switch, and (v) switching the measurement electrode back to a second voltage line; and
(d) calculating the current of each of the electrodes of the measurement set.
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Accused Products
Abstract
There is disclosed a process and apparatus for reading electrical current of electrodes on a microarray of electrodes. Those electrodes having binding events are detected by a difference in electrical current flow. Enzymes on targets catalyze the conversion of substrate to product, which is detectable by electrochemical reduction at each electrode on the microarray of electrodes. The apparatus has an integration circuit that provides a voltage output that is measured and recorded over time and used to calculate an average current flow. A potentiometer equalizes voltage at electrodes undergoing measurement compared to grounded electrodes.
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Citations
27 Claims
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1. A process for reading electrical current of electrodes on a microarray of electrodes comprising the steps of:
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(a) providing a measurement system having a control system, an integration circuit, a microarray chamber, a plurality of voltage lines, an analog to digital converter connected to digital circuitry and analog circuitry, where the analog circuitry includes the integration circuit, where the digital circuitry is separate from the analog circuitry and includes the control system, where the control system, the integration circuit, and the microarray chamber are in circuit communication, where the microarray chamber contains a microarray having a plurality of electrodes in circuit communication with the control system and the integration circuit, where the voltage lines are switchably connectable to each electrode by the control system, where the integration circuit has a capacitance value, where the integration circuit has an integrating transimpedance amplifier having a positive input and a potentiometer circuit connected to the positive input via an operational amplifier; (b) initializing measurement by setting a measurement set of the electrodes to approximately ground, setting a counter electrode voltage of at least one counter electrode, and pausing for a steady state period, where the at least one counter electrode is in fluid communication with the measurement set of the electrodes; (c) measuring the current for each electrode of the measurement set of electrodes by (i) using a first voltage line to connect a measurement electrode to the integration circuit, the integration circuit having a reset switch, where the reset switch is in the closed position, (ii) pausing for an electrode settling period, (iii) opening the reset switch to measure and record a voltage response from the output of the integration circuit for a measurement time at a sampling rate, (iv) closing the reset switch, and (v) switching the measurement electrode back to a second voltage line; and (d) calculating the current of each of the electrodes of the measurement set. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A process for reading electrical current of electrodes on a microarray of electrodes comprising the steps of:
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(a) providing a measurement system having a control system, an integration circuit, a microarray chamber, a plurality of voltage lines, an analog to digital converter, digital circuitry, and analog circuitry, where the analog circuitry includes the integration circuit, where the analog to digital converter transfers the output of the analog circuitry to the digital circuitry, where the digital circuitry is separate from the analog circuitry and includes the control system, where the control system, the integration circuit, and the microarray chamber are in circuit communication, where the microarray chamber contains a microarray having a plurality of electrodes in circuit communication with the control system and the integration circuit, where the voltage lines are switchably connectable to each electrode by the control system, where the integration circuit has an integrating transimpedance amplifier having a positive input and a potentiometer circuit connected to the positive input via an operational amplifier; (b) initializing measurement by setting a measurement set of the electrodes to approximately ground, setting a counter electrode voltage of at least one counter electrode, and pausing for a steady state period, where the at least one counter electrode is in fluid communication with the measurement set of the electrodes; (c) measuring the current for each electrode of the measurement set of electrodes current by (i) using a first voltage line a to connect connecting a measurement electrode to the integration circuit, the integration circuit where the reset switch is in the closed position, (ii) pausing for an electrode settling period, (iii) opening the reset switch to measure and record a voltage response from the output of the integration circuit for a measurement time at a sampling rate, (iv) closing the reset switch, and (v) switching the measurement electrode back to a second voltage line; and (d) calculating the current of each of the electrodes of the measurement set, where calculating the current of each electrode is carried out using linear regression of the voltage response and measurement time, where the linear regression analysis results in a correlation between the voltage response and the measurement time, there the correlation has a slope, where the current is equal to the negative of the slope multiplied by the capacitor value. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26)
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27. A process for reading electrical current of electrodes on a microarray of electrodes comprising the steps of:
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(a) providing a measurement system having a control system, an integration circuit, a microarray chamber, a plurality of voltage lines, an analog to digital converter, digital circuitry, and analog circuitry, where the analog circuitry includes the integration circuit, where the analog to digital converter transfers the output of the analog circuitry to the digital circuitry, where the digital circuitry is separate from the analog circuitry and includes the control system, where the control system, the integration circuit, and the microarray chamber are in circuit communication, where the microarray chamber contains a microarray having a plurality of electrodes in circuit communication with the control system and the integration circuit, where the voltage lines are switchably connectable to each electrode by the control system, where the integration circuit has a capacitance value, where the integration circuit has an integrating transimpedance amplifier having a positive input and a potentiometer circuit connected to the positive input via an operational amplifier; (b) initializing measurement by setting a measurement set of the electrodes to approximately ground, setting a counter electrode voltage of at least one counter electrode, and pausing for a steady state period, where the at least one counter electrode is in fluid communication with the measurement set of the electrodes; (c) measuring the current for each electrode of the measurement set of electrodes current by (i) using a first voltage line a to connect connecting a measurement electrode to the integration circuit, the integration circuit where the reset switch is in the closed position, (ii) pausing for an electrode settling period, (iii) opening the reset switch to measure and record a voltage response from the output of the integration circuit for a measurement time at a sampling rate, (iv) closing the reset switch, and (v) switching the measurement electrode back to a second voltage line; and (d) calculating the current of each of the electrodes of the measurement set, where calculating the current of each electrode is carried out using linear regression of the voltage response and measurement time, where the linear regression analysis results in a correlation between the voltage response and the measurement time, there the correlation has a slope, where the current is equal to the negative of the slope multiplied by the capacitor value.
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Specification