# US 12,216,079 B2 · Sensor circuit for controlling, detecting, and measuring a molecular complex

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- Number: US 12,216,079 B2
- Document ID: US12216079B2
- Status: Granted
- Kind: B2
- Application number: 17/651,766
- Filed: 2022-02-18
- Published: 2022-06-02
- Granted: 2025-02-04
- Earliest claimed: 2012-02-27
- Assignees: Roche Sequencing Solutions, Inc.
- Applicants: Roche Sequencing Solutions, Inc.
- Inventors: Kevin Deierling; Roger J. A. Chen; David J. Fullagar
- Web page: https://patentgrep.com/patent/US12216079B2

## CPC

- G01N 27/4473: {by electric means}
- C12Q 1/6869: Methods for sequencing
- C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation
- G01N 27/44782: {of a plurality of samples}
- G01N 27/44791: {Microapparatus (sample containers with integrated microfluidic structures B01L3/5027)}
- G01N 33/48721: {Investigating individual macromolecules, e.g. by translocation through nanopores (Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68)}
- Y10T 436/11: Automated chemical analysis
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

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.

## Claims

### Claim 1

A device, the device comprising:
a plurality of measurement cells, each measurement cell including a cell electrode above which a nanopore is formed, the cell electrode configurable to apply a distinct potential that is independent from cell electrodes in other measurement cells, the plurality of measurement cells comprising a bank of M×N measurement cells, wherein M refers to a number rows and N refers to a number of columns in the bank of measurement cells; and
a single common electrode configured to be in electrical communication with each cell electrode of the plurality of measurement cells, the single common electrode configured to apply a common potential to a liquid on one side of the nanopores formed above the cell electrodes in the plurality of measurement cells, wherein the common potential is common to all of the measurement cells, wherein a potential across the nanopore in the measurement cell is a difference between the distinct potential applied by the cell electrode of the measurement cell and the common potential applied by the single common electrode.

### Claim 2 (depends on 1)

The device of claim 1, wherein the bank is a complete sub-system with row and column addressing logic.

### Claim 3 (depends on 1)

The device of claim 1, wherein the bank includes a double buffered output.

### Claim 4 (depends on 1)

The device of claim 1, wherein the bank includes a read path and a write path, and wherein the read path and the write paths are separate and operate in a time multiplexed fashion.

### Claim 5 (depends on 1)

The device of claim 1, wherein the bank includes a plurality of analog-to-digital converters.

### Claim 6 (depends on 5)

The device of claim 5, wherein each measurement cell includes an integrator electronically coupled to the cell electrode, and wherein the integrator in each measurement cell measures the current flowing between the single common electrode and the cell electrode in the measurement cell.

### Claim 7 (depends on 6)

The device of claim 6, 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.

### Claim 8 (depends on 7)

The device of claim 7, wherein each measurement cell further includes a liquid chamber containing the liquid, and wherein,
is the single common electrode supplies a common electric potential when the liquid chamber contains an electrolyte,
the cell electrode supplies a variable electric potential when the liquid chamber contains the electrolyte, wherein the voltage between the single common electrode and the cell electrode equals the variable electric potential minus the common electric potential,
the integrator includes an integrating capacitor, the voltage across the integrating capacitor is a measure of the current flowing between the single common electrode and the cell electrode during a measurement period, and
the variable electric potential of the cell electrode is controlled by an applied voltage.

### Claim 9 (depends on 7)

The device of claim 7, wherein the analog-to-digital converter coupled to the integrator measures a first voltage at an output of the integrator at a beginning of the measurement period and a second voltage at the output of the integrator at an end of the measurement period, and wherein a difference of the second voltage and the first voltage corresponds to a measurement of the current.

### Claim 10 (depends on 9)

The device of claim 9, wherein the measurement period is adjusted based at least in part on the current and how much time the current would take to cause a saturation.

### Claim 11

A method of constructing a nanopore based sequencing system, the method comprising:
providing a plurality of measurement cells, each measurement cell including a cell electrode above which a nanopore is formed, the cell electrode configurable to apply a distinct potential that is independent from cell electrodes in other measurement cells, the plurality of is measurement cells comprising a bank of M×N measurement cells, wherein M refers to a number rows and N refers to a number of columns in the bank of measurement cells; and
providing a single common electrode configured to be in electrical communication with each cell electrode of the plurality of measurement cells, the single common electrode configured to apply a common potential to a liquid on one side of the nanopores formed above the cell electrodes in the plurality of measurement cells, wherein the common potential is common to all of the measurement cells, wherein a potential across the nanopore in the measurement cell is a difference between the distinct potential applied by the cell electrode of the measurement cell and the common potential applied by the single common electrode.

### Claim 12 (depends on 11)

The method of claim 11, wherein the bank is a complete sub-system with row and column addressing logic.

### Claim 13 (depends on 11)

The method of claim 11, wherein the bank includes a double buffered output.

### Claim 14 (depends on 11)

The method of claim 11, wherein the bank includes a read path and a write path, and wherein the read path and the write paths are separate and operate in a time multiplexed fashion.

### Claim 15 (depends on 11)

The method of claim 11, wherein the bank includes a plurality of analog-to-digital converters.

### Claim 16 (depends on 15)

The method of claim 15, wherein each measurement cell includes an integrator electronically coupled to the cell electrode, and wherein the integrator in each measurement cell measures the current flowing between the single common electrode and the cell electrode in the measurement cell.

### Claim 17 (depends on 16)

The method of claim 16, 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.

### Claim 18 (depends on 17)

The method of claim 17, wherein each measurement cell further includes a liquid chamber containing the liquid, and wherein,
the single common electrode supplies a common electric potential when the liquid chamber contains an electrolyte,
the cell electrode supplies a variable electric potential when the liquid chamber contains the electrolyte, wherein the voltage between the single common electrode and the cell electrode equals the variable electric potential minus the common electric potential,
the integrator includes an integrating capacitor, the voltage across the integrating capacitor is a measure of the current flowing between the single common electrode and the cell electrode during a measurement period, and
the variable electric potential of the cell electrode is controlled by an applied voltage.

### Claim 19 (depends on 17)

The method of claim 17, wherein the analog-to-digital converter coupled to the integrator measures a first voltage at an output of the integrator at a beginning of the measurement period and a second voltage at the output of the integrator at an end of the measurement period, and wherein a difference of the second voltage and the first voltage corresponds to a measurement of the current.

### Claim 20 (depends on 19)

The method of claim 19, wherein the measurement period is adjusted based at least in part on the current and how much time the current would take to cause a saturation.
