Multiplexing analog components in biochemical sensor arrays
AssigneeRoche Sequencing Solutions, Inc.
InventorJ. William Maney, Jr.
Life of this patent
Estimating the term…
Abstract
Techniques for increasing the density and the number of cells on a nanopore sensor chip are disclosed. Two or more cells of the nanopore sensor chip share some analog components (e.g., an integration capacitor and/or a read-out transistor) through one or more digital relays. Under the control of various control signals during a sampling period of the sensor chip, the two or more cells are connected one at time to the shared analog components and are measured one at a time using the shared analog components. In this way, the average size of the cells on the sensor chip is reduced to increase the cell density without affecting the analog measurement performance of the cells.
Claims20
A sensor chip for nucleic acid sequencing, the sensor chip comprising:
- a set of cells, each cell configured to support a nanopore disposed in a membrane;
- a read-out bus for the set of cells;
- a shared analog measurement circuit in electrical communication with the set of cells, wherein the shared analog measurement circuit comprises one or more components and a connect switch that connects the one or more components to an analog-to-digital converter through the read-out bus;
- a set of cell selection switches in electrical communication with both the set of cells and the shared analog measurement circuit;
- and
- a controller programmed to:
- activate, based on a cell selection signal, a cell selection switch corresponding to a cell of the set of cells during a periodic sampling period of the sensor chip to connect the cell to the shared analog measurement circuit;
- sample for a measurement time using the shared analog measurement circuit an electrical signal generated from the cell;
- activate, based on a row selection signal, the connect switch to connect the shared analog measurement circuit to the analog-to-digital converter;
- send the sampled electrical signal to the read-out bus through the connect switch;
- and
- repeat the activations, the sampling, and the sending for another cell of the set of cells during the periodic sampling period.
A method of nucleic acid sequencing using a sensor chip that includes (i) a set of nanopore cells each configured to support a nanopore disposed in a membrane and (ii) a set of cell selection switches in electrical communication with both the set of nanopore cells and one or more components of a shared analog measurement circuit, the method comprising:
- connecting, through a first cell selection switch based on a first cell selection signal, a first nanopore cell of the set of nanopore cells to the shared analog measurement circuit, wherein the shared analog measurement circuit is between the set of nanopore cells and a read-out bus of the sensor chip, wherein the first cell selection switch is activated by a controller of the sensor chip;
- generating, at the shared analog measurement circuit, a first signal associated with a state of the nanopore of the first nanopore cell;
- measuring, via the read-out bus and a connect switch connecting the shared analog measurement circuit to an analog-to-digital converter through the read-out bus, the first signal generated at the shared analog measurement circuit;
- disconnecting the first nanopore cell from the shared analog measurement circuit;
- connecting, through a second cell selection switch based on a second cell selection signal, a second nanopore cell of the set of nanopore cells to the shared analog measurement circuit;
- generating, at the shared analog measurement circuit, a second signal associated with a state of the nanopore of the second nanopore cell;
- measuring, via the read-out bus and the connect switch, the second signal generated at the shared analog measurement circuit;
- and
- disconnecting the second nanopore cell from the shared analog measurement circuit.
A method of nucleic acid sequencing using a sensor chip that includes (i) a set of nanopore cells each configured to support a nanopore disposed in a membrane and (ii) a set of cell selection switches in electrical communication with both the set of nanopore cells and one or more components of a shared analog measurement circuit, the method comprising, for each nanopore cell of the set of nanopore cells:
- connecting the nanopore cell to the shared analog measurement circuit through a cell selection switch of the set of cell selection switches corresponding to the nanopore cell based on a cell selection signal, wherein the shared analog measurement circuit is between the set of nanopore cells and a read-out bus of the sensor chip, and wherein the cell selection switch of the set of cell selection switches is activated by a controller of the sensor chip;
- generating, at the shared analog measurement circuit, a signal associated with a state of the nanopore of the nanopore cell;
- measuring, via the read-out bus and a connect switch connecting the shared analog measurement circuit to an analog-to-digital converter through the read-out bus, the signal generated at the shared analog measurement circuit;
- and
- disconnecting the nanopore cell from the shared analog measurement circuit.
A method of nucleic acid sequencing using a sensor chip that includes (i) a set of nanopore cells each configured to support a nanopore disposed in a membrane and (ii) a set of cell selection switches in electrical communication with both the set of nanopore cells and one or more components of a shared analog measurement circuit, the method comprising:
- connecting, through a first cell selection switch based on a first cell selection signal, a first nanopore cell of the set of nanopore cells to the shared analog measurement circuit, wherein:
- the sensor chip includes a read-out bus for the set of nanopore cells;
- the shared analog measurement circuit is connected to an analog-to-digital converter through the read-out bus and a connect switch and is configured to be connected to the set of nanopore cells one at a time;
- and
- the first cell selection switch is activated by a controller of the sensor chip;
- measuring, using the shared analog measurement circuit, a first signal associated with a state of the nanopore of the first nanopore cell;
- disconnecting the first nanopore cell from the shared analog measurement circuit;
- connecting a second nanopore cell of the set of nanopore cells to the shared analog measurement circuit;
- measuring, using the shared analog measurement circuit, a second signal associated with a state of the nanopore of the second nanopore cell;
- and
- disconnecting the second nanopore cell from the shared analog measurement circuit.
Dependencies are inferred from the claim text.