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US 2015/0337367 A1Published application
High density nanopore polynucleotide sequencer
AssigneeThe Regents of the University of California
InventorsJungsuk Kim, William Dunbar
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Abstract
A polynucleotide sequencer comprising an integrated and multiplexed network of patch clamp capacitive integrator-differentiator amplifiers with small feedback capacitors using pseudo-resistors.
Claims26
A method comprising:
- measuring, with each of at least one measuring device, an ionic current produced by each of at least one molecule;
- connecting the each of the at least one measuring device to each of at least one first operational amplifier;
- connecting the at least one first operational amplifier to at least one second operational amplifier;
- configuring the at least one first operational amplifier and the at least one second operational amplifier to amplify the ionic current measured by the at least one measuring device;
- and
- wherein the first operational amplifier and the second operational amplifier are configured to be a capacitive feedback transimpedance amplifier, the method further comprising connecting the at least one second operational amplifier to a computing device and wherein measuring with each of the at least one measuring device comprises:
- loading each of the at least one molecule in a first chamber of each of at least one measuring device;
- applying a first voltage to the first chamber of each of the at least one measuring device;
- applying a second voltage to a second chamber of each of the at least one measuring device;
- attracting each of the at least one molecule with the first voltage and the second voltage such that each of the at least one molecule moves from the first chamber to the second chamber of each of the at least one measuring device;
- and
- measuring, with a sensing unit of each of the at least one measuring device, the ionic current caused by the movement of each of the at least one molecule
- and wherein the each of the at least one first operational amplifier is connected to one of the at least one second operational amplifier.
10 more elements
2-8. (canceled)
(canceled)
An apparatus comprising:
- at least one measuring device configured to measure an ionic current produced by each of at least one polynucleotide molecule;
- each of at least one first operational amplifier configured to accept a first output of each of the at least one measuring device;
- and
- at least one second operational amplifier configured to accept one or more second output of each of the at least one first operational amplifier, wherein the each of the at least one first operational amplifier and the each of the at least one second operational amplifier are configured to amplify the ionic current measured by the at least one measuring device;
- wherein the first operational amplifier and the second operational amplifier are configured to be a resistive feedback transimpedance amplifier, wherein the apparatus further comprises a computing device configured to receive a third output of the at least one second operational amplifier, and wherein each of the at least one measuring device further comprises:
- (i) a first chamber of each of at least one measuring device configured to receive each of the at least one polynucleotide molecule;
- (ii) a means for applying a first voltage to the first chamber of each of the at least one measuring device;
- (iii) a means for applying a second voltage to a second chamber of each of the at least one measuring device;
- (iv) a means for attracting each of the at least one polynucleotide molecule with the first voltage and the second voltage such that each of the at least one polynucleotide molecule moves from the first chamber to the second chamber of each of the at least one measuring device;
- and
- a sensing unit of each of the at least one measuring device configured to measure the ionic current caused by the movement of each of the at least one molecule.
8 more elements
12-14. (canceled)
16-17. (canceled)
19-25. (canceled)
A patch clamp amplifier, comprising:
- an integrating operational amplifier having a first inverting input for receiving current from a nanopore sensor, said integrating operational amplifier further having a first non-inverting input and a first output;
- a feedback capacitor connecting said first output to said first inverting input;
- a feedback impendence in parallel with said feedback capacitor;
- a differentiator operational amplifier having a second inverting input, a second non-inverting input, and a second output;
- a first input capacitor connecting said second inverting input to said first output;
- a first input impedance in parallel with said first input capacitor;
- a second input capacitor connecting said second non-inverting input to said first non-inverting input;
- a second input impedance in parallel with said second input capacitor;
- a first resistor connecting said second output to said second inverting input;
- and
- a second resistor connecting said second non-inverting input to ground;
- wherein said feedback impedance is a pseudo-resistor.
9 more elements
A multiplexed nanopore sensing network on a semiconductor chip, comprising:
- an integrating first operational amplifier;
- an integrating second operational amplifier;
- an integrating third operational amplifier;
- a multiplexer receiving the output of said first operational amplifier, and receiving the output of said second operational amplifier, and receiving the output of said third operational amplifier, wherein when in use said multiplexer outputs the output of said first operational amplifier when first control data is received, and outputs the output of said second operational amplifier when second control data is received, and outputs the output of said third operational amplifier when third control data is received;
- a differentiator operational amplifier that receives and differentiates said output of said multiplexer into a differentiated output;
- an analog to digital converter that converts said differentiated output into a digital signal;
- and
- a multiplexing control block adapted to selectively apply said first control data, said second control data, and said third control data to said multiplexer.
5 more elements
40-45. (canceled)
Dependencies are inferred from the claim text.