Sensor circuit for controlling, detecting, and measuring a molecular complex
A device for controlling, detecting, and measuring a molecular complex is disclosed. The device comprises a common electrode. The device further comprises a plurality of measurement cells. Each measurement cell includes a cell electrode and an integrator electronically coupled to the cell electrode. The integrator measures the current flowing between the common electrode and the cell electrode. The device further comprises a plurality of analog-to-digital converters, wherein an integrator from the plurality of measurement cells is electrically coupled to one analog-to-digital converter of the plurality of analog-to-digital converters.
1. A device, the device comprising:
a precharging voltage source;
a first cell electrode;
a second electrode, the second electrode configured to apply a liquid potential to a liquid in contact with a nanopore positioned electrically between the first cell electrode and the second electrode;
a capacitor electronically coupled to the first cell electrode;
an electronic switch that selectively couples the capacitor to the precharging voltage source;
an analog-to-digital converter electrically coupled to the capacitor; and
a processor programmed to:
send a precharge signal to the electronic switch to close the electronic switch and electrically couple the capacitor to the precharging voltage source;
precharge the capacitor to a set voltage at a beginning of a measurement period;
send a signal to the electronic switch to open the electronic switch to decouple the capacitor from the precharging voltage source; and
measure a decay in voltage across the capacitor during the measurement period using the analog-to-digital converter.
2. The device of claim 1 , further comprising a liquid chamber containing the liquid.
3. The device of claim 2 , wherein
the second electrode supplies the liquid potential when the liquid chamber contains an electrolyte;
the first cell electrode supplies a variable electric potential when the liquid chamber contains the electrolyte, wherein a voltage between the second electrode and the first cell electrode equals the variable electric potential minus the liquid potential; and
the decay in voltage across the capacitor is a function of a resistance through the nanopore.
4. The device of claim 3 , wherein,
the device is configured to detect a physical state and transpose the physical state from a plurality of possible physical states of a material in the liquid chamber, by modulating the voltage between the second electrode and the first cell electrode and measuring a voltage decay between the first cell electrode and the second electrode, and
the plurality of possible physical states comprises:
no formation of a lipid bilayer,
formation of a lipid bilayer,
insertion of a nanopore protein in a lipid bilayer, forming a nanopore, and
interaction of a molecular complex with the nanopore.
5. The device of claim 2 , wherein the device is configured to retain at least one lipid, one nanopore protein, and one molecular complex in the liquid chamber.
6. The device of claim 5 , wherein the device is configured to recognize a specific base type corresponding to the molecular complex in the liquid chamber by using the measurement of the decay in voltage across the capacitor.
7. The device of claim 1 , further comprising
a buffering component that is electrically coupled to the analog-do-digital converter to buffer an output of the capacitor before being connected to the analog-do-digital converter.
8. The device of claim 1 , wherein the analog-to-digital converter electrically coupled to the capacitor measures a first voltage at an output of the capacitor at the beginning of the measurement period and a second voltage at the output of the capacitor at an end of the measurement period, and wherein a difference of the second voltage and the first voltage corresponds to the measurement of the decay in voltage across the capacitor.
9. The device of claim 8 , wherein the measurement period is set or predetermined and remains fixed between measurements.
10. The device of claim 1 , wherein the analog-to-digital converter includes a comparator.
11. The device of claim 10 , wherein the analog-to-digital converter includes a controlling analog input, and the controlling analog input controls a variable sample rate of a current flowing between the first cell electrode and the second electrode by varying a voltage at the controlling analog input.
12. The device of claim 11 , wherein the variable sample rate increases when the current flowing between the first cell electrode and the second electrode increases.
13. The device of claim 11 , wherein the varied voltage comprises a comparator threshold.
14. The device of claim 11 , wherein the varied voltage comprises an initial voltage at an output of the capacitor.
15. A device, the device comprising:
a precharging voltage source;
a first cell electrode;
a second electrode, the second electrode configured to apply a liquid potential to a liquid in contact with a nanopore positioned electrically between the first cell electrode and the second electrode;
a capacitor electronically coupled to the first cell electrode;
an electronic switch that selectively couples the capacitor to the precharging voltage source;
an analog-to-digital converter electrically coupled to the capacitor; and
a processor programmed to:
send a precharge signal to the electronic switch to close the electronic switch and electrically couple the capacitor to the precharging voltage source;
precharge the capacitor to a set voltage at a beginning of a measurement period;
send a signal to the electronic switch to open the electronic switch to decouple the capacitor from the precharging voltage source; and
measure a decay in voltage across the capacitor during the measurement period using the analog-to-digital converter, wherein the measurement period is set or predetermined and remains fixed between measurements.
16. A device, the device comprising:
a precharging voltage source;
a first cell electrode;
a second electrode, the second electrode configured to apply a liquid potential to a liquid in contact with a nanopore positioned electrically between the first cell electrode and the second electrode;
a capacitor electronically coupled to the first cell electrode;
an electronic switch that selectively couples the capacitor to the precharging voltage source;
an analog-to-digital converter electrically coupled to the capacitor; and
a processor programmed to:
send a precharge signal to the electronic switch to close the electronic switch and electrically couple the capacitor to the precharging voltage source;
precharge the capacitor to a set voltage at a beginning of a measurement period;
send a signal to the electronic switch to open the electronic switch to decouple the capacitor from the precharging voltage source; and
measure a decay in voltage across the capacitor during the measurement period using the analog-to-digital converter, wherein the measurement period is determined based on a time for the measured decay in voltage across the capacitor to reach a fixed magnitude.