Capacitive feedback (transimpedance) amplifier for use with nanopore detection and sequencing device

Abstract

A multiplexed nanopore sensing network comprising an integrated and multiplexed network of patch clamp capacitive integrator-differentiator amplifiers with small feedback capacitors using pseudo-resistors.

1 . A multiplexed nanopore sensing network, comprising:
 (i) an integrating first operational amplifier;   (ii) an integrating second operational amplifier;   (iii) an integrating third operational amplifier;   
       wherein at least one of said integrating operational amplifiers comprises:
 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 impedance 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 provided by a pseudo-resistor or an on-chip poly resistor, and 
 (iv) 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; 
 (v) a differentiator operational amplifier that receives and differentiates said output of said multiplexer into a differentiated output; 
 (vi) an analog to digital converter that converts said differentiated output into a digital signal; and 
 (vii) a multiplexing control block adapted to selectively apply said first control data, said second control data, and said third control data to said multiplexer. 
 
     
     
         2 . The multiplexed nanopore sensing network according to  claim 1 , wherein said integrating first operational amplifier and said differentiator operational amplifier are compensated. 
     
     
         3 . The multiplexed nanopore sensing network according to  claim 1 , wherein said integrating first operational amplifier is a resistive feedback amplifier having a feedback resistance. 
     
     
         4 . The multiplexed nanopore sensing network according to  claim 3 , wherein said feedback resistance is controlled by a pseudo-resistor. 
     
     
         5 . The multiplexed nanopore sensing network according to  claim 1 , wherein said integrating first operational amplifier is a capacitive feedback amplifier having a feedback capacitor. 
     
     
         6 . The multiplexed nanopore sensing network according to  claim 5 , wherein said feedback capacitor is in parallel with a feedback impedance. 
     
     
         7 . The multiplexed nanopore sensing network according to  claim 6 , wherein said feedback impedance is applied by a pseudo-resistor. 
     
     
         8 . The multiplexed nanopore sensing network according to  claim 1 , wherein said multiplexing control block outputs a system clock, and wherein said multiplexing control block only applies control data output once per system clock. 
     
     
         9 . The multiplexed nanopore sensing network according to  claim 1 , further including:
 a first nanopore sensor inputting a first signal into said integrating first operational amplifier;   a second nanopore sensor inputting a second signal into said integrating second operational amplifier; and   a third nanopore sensor inputting a third signal into said integrating third operational amplifier;   wherein said first nanopore sensor, said second nanopore sensor, said third nanopore senor and said multiplexer share a common ground.   
     
     
         10 . The multiplexed nanopore sensing network according to  claim 1 , wherein said integrating first operational amplifier includes:
 an input pad having a first metal layer;   an ESD circuit; and   an operational amplifier;   wherein said ESD circuit and said operational amplifier are located directly below said input pad.   
     
     
         11 . The multiplexed nanopore sensing network according to  claim 1  comprising at least 2000 nanopore sensors. 
     
     
         12 . The multiplexed nanopore sensing network according to  claim 1  comprising at least 10000 nanopore sensors.