Abstract: A method of forming a plurality of lipid bilayers over an array of cells in a nanopore based sequencing chip is disclosed. Each of the cells comprises a well. A salt buffer solution is flowed over the array of cells in the nanopore based sequencing chip to substantially fill the wells in the cells with the salt buffer solution. A lipid and solvent mixture is flowed over the array of cells to deposit the lipid and solvent mixture over at least some of the wells in the cells. A first portion of the cells, each having a lipid bilayer over its well, is detected. A second portion of the cells, each having a lipid membrane but not a lipid bilayer over its well, is detected. An electrical lipid-thinning stimulus is selectively applied to the second portion of the cells but not to the first portion of the cells.

Abstract: A method of forming a plurality of lipid bilayers over an array of cells in a nanopore based sequencing chip is disclosed. Each of the cells comprises a well. A salt buffer solution is flowed over the array of cells in the nanopore based sequencing chip to substantially fill the wells in the cells with the salt buffer solution. A lipid and solvent mixture is flowed over the array of cells to deposit the lipid and solvent mixture over at least some of the wells in the cells. A first portion of the cells, each having a lipid bilayer over its well, is detected. A second portion of the cells, each having a lipid membrane but not a lipid bilayer over its well, is detected. An electrical lipid-thinning stimulus is selectively applied to the second portion of the cells but not to the first portion of the cells.

Abstract: Techniques described herein can apply AC signals with different phases to different groups of nanopore cells in a nanopore sensor chip. When a first group of nanopore cells is in a dark period and is not sampled or minimally sampled by an analog-to-digital converter (ADC) to capture useful data, a second group of nanopore cells is in a bright period during which output signals from the second group of nanopore cells are sampled by the analog-to-digital converter. The reference level setting of the ADC is dynamically changed based on the applied AC signals to fully utilize the dynamic range of the ADC.

Abstract: Systems and methods for inserting a single pore into a membrane under faradaic conditions are described herein. A stepped or ramped voltage waveform can be applied across the membranes of the cells of an array, where the voltage waveform starts at first voltage and increases in magnitude over a period of time to a second voltage. The voltage waveform has a polarity that maintains a first species of a redox couple in its current oxidation state. The first voltage is selected to be low enough to reduce the risk of damaging the membrane, while the rate of voltage increase is selected to provide sufficient time for the pores to insert into the membranes. Once a pore is inserted into the membrane, the voltage across the membrane rapidly drops, thereby reducing the risk of damaging the membrane even if the applied voltage between the electrodes is further increased.

Abstract: A nanopore-based sequencing chip can have a surface with an array of wells, with each well having a working electrode. Charge can be established within the wells by applying a voltage between the working electrodes and a counter electrode. The charge can then be trapped within the wells by sealing the wells with a membrane. The trapped charge can be used to facilitate pore insertion into the membranes.

Abstract: Techniques described herein can apply AC signals with different phases to different groups of nanopore cells in a nanopore sensor chip. When a first group of nanopore cells is in a dark period and is not sampled or minimally sampled by an analog-to-digital converter (ADC) to capture useful data, a second group of nanopore cells is in a bright period during which output signals from the second group of nanopore cells are sampled by the analog-to-digital converter. The reference level setting of the ADC is dynamically changed based on the applied AC signals to fully utilize the dynamic range of the ADC.

Abstract: A system includes a plurality of nanopore cells. Data corresponding to nanopore states of the plurality of nanopore cells is received. The data is analyzed to determine a compressed output size of the data given at least one compression technique. It is determined whether the compressed output size exceeds a data budget. In the event it is determined that the compressed output size exceeds the data budget, the data is modified. The modified data is outputted.

Abstract: A nanopore based sequencing chip package is disclosed. The nanopore based sequencing chip package includes a reservoir defined by a plurality of surfaces. The chip package includes a nanopore cell array comprising a plurality of nanopore sensor cells enclosed by the reservoir. Each nanopore sensor cell has a working electrode. At least one surface of the reservoir is configured to be in contact with a conducting fluid when the conducting fluid is flowing through the reservoir. The chip package further includes a counter electrode disposed on the at least one surface of the reservoir.

Abstract: A system includes a plurality of nanopore cells. Data corresponding to nanopore states of the plurality of nanopore cells is received. The data is analyzed to determine a compressed output size of the data given at least one compression technique. It is determined whether the compressed output size exceeds a data budget. In the event it is determined that the compressed output size exceeds the data budget, the data is modified. The modified data is outputted.

Abstract: A method of analyzing a molecule in a nanopore is disclosed. A voltage is applied across a nanopore that is inserted in a membrane by coupling the nanopore to a voltage source. The nanopore is decoupled from the voltage source. After the decoupling, a rate of decay of the voltage across the nanopore is determined. A molecule in the nanopore is distinguished from other possible molecules based on the determined rate of decay of the voltage across the nanopore.

Abstract: A method of analyzing a molecule is disclosed. A voltage source is selectively connected to or disconnected from a capacitor using a switch controlled by a reset signal. A charge is stored in a capacitor when the voltage source is connected to the capacitor. The capacitor is discharged through a nanopore in a membrane when the voltage source is disconnected from the capacitor. A duty cycle of the reset signal is determined such that the voltage source and the capacitor is connected for at least a one tenth portion of a reset signal period and disconnected for a remaining portion of the reset signal period, such that a voltage across the nanopore is maintained at a higher level during the portion of the reset signal period in which the connection is maintained than during the remaining portion of the reset signal period in which the connection is not maintained.

Abstract: A method of analyzing a molecule in a nanopore is disclosed. A voltage is applied across a nanopore that is inserted in a membrane by coupling the nanopore to a voltage source. The nanopore is decoupled from the voltage source. After the decoupling, a rate of decay of the voltage across the nanopore is determined. A molecule in the nanopore is distinguished from other possible molecules based on the determined rate of decay of the voltage across the nanopore.

Abstract: A method of forming a plurality of lipid bilayers over an array of cells in a nanopore based sequencing chip is disclosed. Each of the cells comprises a well. A salt buffer solution is flowed over the array of cells in the nanopore based sequencing chip to substantially fill the wells in the cells with the salt buffer solution. A lipid and solvent mixture is flowed over the array of cells to deposit the lipid and solvent mixture over at least some of the wells in the cells. A first portion of the cells, each having a lipid bilayer over its well, is detected. A second portion of the cells, each having a lipid membrane but not a lipid bilayer over its well, is detected. An electrical lipid-thinning stimulus is selectively applied to the second portion of the cells but not to the first portion of the cells.

Abstract: Systems and methods for inserting a single pore into a membrane are described herein. A stepped or ramped voltage waveform can be applied across the membranes of the cells of an array, where the voltage waveform starts at first voltage and increases in magnitude over a period of time to a second voltage. The first voltage is selected to be low enough to reduce the risk of damaging the membrane, while the rate of voltage increase is selected to provide sufficient time for the pores to insert into the membranes. Once a pore is inserted into the membrane, the voltage across the membrane rapidly drops, thereby reducing the risk of damaging the membrane even if the applied voltage between the electrodes is further increased.

Abstract: A method of analyzing a molecule is disclosed. A voltage source is selectively connected to or disconnected from a capacitor using a switch controlled by a reset signal. A charge is stored in a capacitor when the voltage source is connected to the capacitor. The capacitor is discharged through a nanopore in a membrane when the voltage source is disconnected from the capacitor. A duty cycle of the reset signal is determined such that the voltage source and the capacitor is connected for at least a one tenth portion of a reset signal period and disconnected for a remaining portion of the reset signal period, such that a voltage across the nanopore is maintained at a higher level during the portion of the reset signal period in which the connection is maintained than during the remaining portion of the reset signal period in which the connection is not maintained.

Abstract: A liquid voltage is applied to a first side of a lipid bilayer. The liquid voltage comprises a tag-reading period with a tag-reading voltage that tends to capture a tag into a nanopore in the lipid bilayer and an open-channel period with an open-channel voltage that tends to repel the tag. A pre-charging voltage source is connected to an integrating capacitor and a working electrode on a second side of the lipid bilayer during a pre-charging time period, such that the integrating capacitor and the working electrode are charged to a pre-charging voltage. The pre-charging voltage source is disconnected from the integrating capacitor and the working electrode during an integrating time period, such that a voltage of the integrating capacitor and a voltage of the working electrode may vary as a current flows through the nanopore. The pre-charging time period overlaps with a beginning portion of the tag-reading period.

Abstract: Techniques described herein can apply AC signals with different phases to different groups of nanopore cells in a nanopore sensor chip. When a first group of nanopore cells is in a dark period and is not sampled or minimally sampled by an analog-to-digital converter (ADC) to capture useful data, a second group of nanopore cells is in a bright period during which output signals from the second group of nanopore cells are sampled by the analog-to-digital converter. The reference level setting of the ADC is dynamically changed based on the applied AC signals to fully utilize the dynamic range of the ADC.

Abstract: A method of forming a plurality of lipid bilayers over an array of cells in a nanopore based sequencing chip is disclosed. Each of the cells comprises a well. A salt buffer solution is flowed over the array of cells in the nanopore based sequencing chip to substantially fill the wells in the cells with the salt buffer solution. A lipid and solvent mixture is flowed over the array of cells to deposit the lipid and solvent mixture over at least some of the wells in the cells. A first portion of the cells, each having a lipid bilayer over its well, is detected. A second portion of the cells, each having a lipid membrane but not a lipid bilayer over its well, is detected. An electrical lipid-thinning stimulus is selectively applied to the second portion of the cells but not to the first portion of the cells.

Abstract: A liquid voltage is applied to a first side of a lipid bilayer. The liquid voltage comprises a tag-reading period with a tag-reading voltage that tends to capture a tag into a nanopore in the lipid bilayer and an open-channel period with an open-channel voltage that tends to repel the tag. A pre-charging voltage source is connected to an integrating capacitor and a working electrode on a second side of the lipid bilayer during a pre-charging time period, such that the integrating capacitor and the working electrode are charged to a pre-charging voltage. The pre-charging voltage source is disconnected from the integrating capacitor and the working electrode during an integrating time period, such that a voltage of the integrating capacitor and a voltage of the working electrode may vary as a current flows through the nanopore. The pre-charging time period overlaps with a beginning portion of the tag-reading period.

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.