# US 2025/0085249 A1 · Differential output of analog memories storing nanopore measurement samples > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0085249 A1 - Document ID: US20250085249A1 - Status: Published application - Kind: A1 - Application number: 18/962,946 - Filed: 2024-11-27 - Published: 2025-03-13 - Earliest claimed: 2015-09-24 - Assignees: Roche Sequencing Solutions, Inc. - Applicants: Roche Sequencing Solutions, Inc. - Inventors: Santiago Fernandez-Gomez; Bill Maney; Hui Tian - Web page: https://patentgrep.com/patent/US20250085249A1 ## CPC - G01N 27/26: by investigating electrochemical variables; by using electrolysis or electrophoresis - B82Y 35/00: Methods or apparatus for measurement or analysis of nanostructures - 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)} - 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) - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES ## Abstract A nanopore measurement circuit includes a first analog memory configured to store a first electrical value corresponding to a first measurement sample of a nanopore and a second analog memory configured to store a second electrical value corresponding to a second measurement sample of the nanopore. The nanopore measurement circuit also includes a measurement circuitry configured to provide an output indicating a difference between the first electrical value of the first analog memory and the second electrical value of the second analog memory. ## Claims ### Claim 1 A biochip, comprising: a plurality of nanopore cells, each nanopore cell associated with a measurement circuit configured to measure an electrical characteristic of the nanopore cell; a plurality of local event detectors, each local event detector comprising a circuit configured to receive an electrical measurement sample from a corresponding measurement circuit of a respective nanopore cell; and an adaptive analyzer configured to periodically receive data from the plurality of local event detectors, modify the data based on state change information related to the plurality of local event detectors, and store the modified data in a buffer for output. ### Claim 2 (depends on 1) The biochip of claim 1, wherein each local event detector is configured to determine a difference between the electrical measurement sample and a stored electrical measurement sample for the respective nanopore cell, and determine a state of the respective nanopore cell based on a magnitude of the difference. ### Claim 3 (depends on 2) The biochip of claim 2, wherein the stored electrical measurement sample corresponds to an open-channel state of the corresponding nanopore. ### Claim 4 (depends on 2) The biochip of claim 2, wherein the local event detector is connected to a state memory that stores the stored electrical measurement sample, and wherein the state memory stores at least one additional reference measurement values corresponding to nanopore states. ### Claim 5 (depends on 2) The biochip of claim 2, wherein the adaptive analyzer generates a bit vector included in the modified data, and wherein each bit of the bit vector corresponds to a different nanopore cell and indicates whether a tag has been inserted into the respective nanopore cell during a current measurement period. ### Claim 6 (depends on 5) The biochip of claim 5, wherein the modified data includes a measurement value for each nanopore cell for which a corresponding bit of the bit vector is set. ### Claim 7 (depends on 1) The biochip of claim 1, wherein data is continuously outputted from the biochip from the buffer at a data output rate. ### Claim 8 (depends on 1) The biochip of claim 1, wherein the adaptive analyzer determines whether to compress the data based on an amount of data in the buffer. ### Claim 9 (depends on 8) The biochip of claim 8, wherein modifying the data comprises, in response to determining that the amount of data in the buffer exceeds a threshold value, removing one or more measurement values from the data and resetting an indicator in a state memory for each of the one or more measurement values. ### Claim 10 (depends on 1) The biochip of claim 1, wherein the adaptive analyzer is configured to randomly drop a portion of the data in order to meet a desired output bandwidth of the biochip. ### Claim 11 A method for outputting data from a biochip including a plurality of nanopore cells, the method comprising: receiving data from a plurality of local event detectors, each local event detector comprising a circuit configured to receive an electrical measurement sample from a corresponding measurement circuit of a respective nanopore cell; modifying the data based on state change information determined by the plurality of local event detectors; and storing the modified data in a buffer for output. ### Claim 12 (depends on 11) The method of claim 11, further comprising generating a bit vector, wherein each bit of the bit vector corresponds to a different nanopore cell and indicates whether a tag has been inserted into the respective nanopore cell during a current measurement period. ### Claim 13 (depends on 12) The method of claim 12, wherein the modified data includes a measurement value for each nanopore cell for which a corresponding bit of the bit vector is set. ### Claim 14 (depends on 11) The method of claim 11, further comprising determining whether to compress the data based on an amount of data in the buffer. ### Claim 15 (depends on 14) The method of claim 14, wherein modifying the data based on state change information comprises, in response to determining that the amount of data in the buffer exceeds a threshold value, removing one or more measurement values from the data and resetting an indicator in a state memory for each of the one or more measurement values. ### Claim 16 (depends on 11) The method of claim 11, wherein modifying the data based on state change information comprises randomly dropping a portion of the data in order to meet a desired output bandwidth of the biochip. ### Claim 17 (depends on 11) The method of claim 11, wherein modifying the data based on state change information comprises selecting a lossy compression technique to be applied to the data. ### Claim 18 A system, comprising: a plurality of nanopore cells, each nanopore cell comprising an electrode connected to an analog measurement circuit for measuring an electrical characteristic of the nanopore cell and a local event detector circuit configured to receive an electrical measurement sample from the analog measurement circuit; at least one adaptive analyzer circuit configured to: periodically receive data from a plurality of local event detector circuits, wherein the data comprises at least one measurement value of an electrical measurement sample collected during a measurement period, modify the data based on state change information, and store the modified data in a buffer for output; and an application specific integrated circuit (ASIC) or field programmable gate array (FPGA) configured to receive the modified data from the buffer. ### Claim 19 (depends on 18) The system of claim 18, wherein the local event detector circuit is configured to determine a difference between the electrical measurement sample and a stored electrical measurement sample, and determine a state of the nanopore cell based on a magnitude of the difference. ### Claim 20 (depends on 18) The system of claim 18, wherein the at least one adaptive analyzer circuit generates a bit vector included in the modified data, and wherein each bit of the bit vector corresponds to a different nanopore cell and indicates whether a tag has been inserted into the respective nanopore cell during a current measurement period.