# US 2014/0190833 A1 · Nanopore Sensing By Local Electrical Potential Measurement > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0190833 A1 - Document ID: US20140190833A1 - Status: Published application - Kind: A1 - Application number: 14/009,348 - Filed: 2011-04-29 - Published: 2014-07-10 - Earliest claimed: 2011-04-04 - Assignees: President and Fellows of Harvard College - Inventors: Charles M. Lieber; Ping Xie - Web page: https://patentgrep.com/patent/US20140190833A1 ## CPC - G01N 27/447: using electrophoresis - B82Y 30/00: Nanotechnology for materials or surface science, e.g. nanocomposites - C12Q 1/6869: Methods for sequencing - 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)} - B82Y 15/00: Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors - G01N 27/4145: {specially adapted for biomolecules, e.g. gate electrode with immobilised receptors} - G01N 27/4146: {involving nanosized elements, e.g. nanotubes, nanowires} - 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 - 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 ## Abstract There is provided a nanopore disposed in a support structure, with a fluidic connection between a first fluidic reservoir and an inlet to the nanopore and a second fluidic connection between a second fluidic reservoir and an outlet from the nanopore first ionic solution of a first buffer concentration is disposed in the first reservoir and a second ionic solution of a second buffer concentration, different than the first concentration, is disposed in the second reservoir, with the nanopore providing the sole path of fluidic communication between the first and second reservoirs. An electrical connection is disposed at a location in the nanopore sensor that develops an electrical signal indicative of electrical potential local to at least one site in the nanopore sensor as an object translocates through the nanopore between the two reservoirs. ## Claims ### Claim 1 A nanopore sensor comprising: a nanopore disposed in a support structure; a fluidic connection between a first fluidic reservoir and an inlet to the nanopore, with a first ionic solution of a first buffer concentration disposed in the first reservoir; a fluidic connection between a second fluidic reservoir and an outlet from the nanopore, with a second ionic solution of a second buffer concentration, different than the first concentration, disposed in the second reservoir, the nanopore providing the sole path of fluidic communication between the first and second reservoirs; and an electrical connection, disposed at a location in the nanopore sensor, that develops an electrical signal indicative of electrical potential local to at least one site in the nanopore sensor as an object translocates through the nanopore between the two reservoir solutions. ### Claim 2 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection is disposed at a sensor location that is in communication with the one of the two reservoir fluidic solutions that is of a lower buffer concentration than the other of the two reservoir fluidic solutions. ### Claim 3 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection is disposed at a sensor location that develops an electrical signal indicative of local electrical potential at one of the inlet to the nanopore and the outlet from the nanopore. ### Claim 4 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection is disposed at a sensor location that develops an electrical signal indicative of a difference between local electrical potential at the inlet to the nanopore and the outlet from the nanopore. ### Claim 5 (depends on 1) The nanopore sensor of claim 1 wherein the nanopore is characterized by a fluidic solution resistance and the reservoir of lower fluidic solution buffer concentration is characterized by a reservoir access resistance that is of the same order of magnitude as the nanopore fluidic solution resistance and that is at least an order of magnitude greater than a reservoir access resistance characteristic of the reservoir of higher fluidic solution buffer concentration. ### Claim 6 (depends on 5) The nanopore sensor of claim 5 wherein the electrical connection is disposed at a sensor location that develops an electrical signal indicative of local electrical potential in the one of the reservoirs that is characterized by a greater reservoir access resistance. ### Claim 7 (depends on 1) The nanopore sensor of claim 1 wherein one of the fluidic solution buffer concentrations is at least about 20 times greater than the other of the fluidic solution buffer concentrations. ### Claim 8 (depends on 1) The nanopore sensor of claim 1 wherein one of the fluidic solution buffer concentrations is at least about 50 times greater than the other of the fluidic solution buffer concentrations. ### Claim 9 (depends on 1) The nanopore sensor of claim 1 wherein one of the fluidic solution buffer concentrations is at least about 100 times greater than the other of the fluidic solution buffer concentrations. ### Claim 10 (depends on 1) The nanopore sensor of claim 1 wherein a difference between the fluidic solution buffer concentration of the first fluidic reservoir and the fluidic solution buffer concentration of the second fluidic reservoir is measured from one of the inlet to the nanopore and the outlet from the nanopore, that is at least about 5 nm. ### Claim 11 (depends on 1) The nanopore sensor of claim 1 wherein a difference between the solution buffer concentration of the first fluidic reservoir and the fluidic solution buffer concentration of the second fluidic reservoir is sufficient to produce a local electrical potential signal that is characterized by a bandwidth of at least about 50 MHz. ### Claim 12 (depends on 1) The nanopore sensor of claim 1 wherein the nanopore is characterized by a diameter that is between about 1 nm and about 5 nm. ### Claim 13 (depends on 1) The graphene nanopore sensor of claim 1 wherein the nanopore is characterized by a diameter that is less than about 2 nm. ### Claim 14 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection is disposed at one of the inlet to the nanopore and the outlet from the nanopore and develops an electrical signal indicative of electrical potential local to one of the nanopore inlet and the nanopore outlet. ### Claim 15 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection is disposed at the nanopore and develops an electrical signal indicative of a difference between electrical potential local to the nanopore inlet and electrical potential local to the nanopore outlet. ### Claim 16 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection comprises an electrical device or device region. ### Claim 17 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection comprises an electrical circuit. ### Claim 18 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection comprises a transistor. ### Claim 19 (depends on 18) The nanopore sensor of claim 18 wherein the electrical connection comprises a field effect transistor. ### Claim 20 (depends on 19) The nanopore sensor of claim 19 wherein the electrical connection comprises a nanowire field effect transistor. ### Claim 21 (depends on 20) The nanopore sensor of claim 20 wherein the nanowire comprises a silicon nanowire. ### Claim 22 (depends on 18) The nanopore sensor of claim 18 wherein the electrical connection comprises a single electron transistor. ### Claim 23 (depends on 18) The nanopore sensor of claim 18 wherein the transistor is disposed on the nanopore support structure. ### Claim 24 (depends on 19) The nanopore sensor of claim 19 wherein the field effect transistor comprises an electronic conduction channel that is disposed at the nanopore. ### Claim 25 (depends on 1) The nanopore sensor of claim 1 wherein the support structure in which the nanopore is disposed comprises a membrane. ### Claim 26 (depends on 1) The nanopore sensor of claim 1 wherein the support structure in which the nanopore is disposed comprises a suspended layer of graphene. ### Claim 27 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection comprises a graphene layer in which the nanopore is disposed. ### Claim 28 (depends on 25) The nanopore sensor of claim 25 wherein the electrical connection comprises a nanowire disposed on the membrane at a location of one of the inlet to the nanopore and the outlet from the nanopore. ### Claim 29 (depends on 1) The nanopore sensor of claim 1 wherein the support structure in which the nanopore is disposed comprises a solid state material. ### Claim 30 (depends on 1) The nanopore sensor of claim 1 wherein the support structure in which the nanopore is disposed comprises a biological material. ### Claim 31 (depends on 1) The nanopore sensor of claim 1 further comprising an electrical connection, between the first fluidic solution and the second fluidic solution, that applies a voltage bias between the inlet to the nanopore and the outlet from the nanopore to electrophoretically drive objects through the nanopore. ### Claim 32 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection develops an electrical signal indicative of an electrical potential local to at least one site in the nanopore sensor in response to a molecule translocating through the nanopore. ### Claim 33 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection develops an electrical signal indicative of an electrical potential local to at least one site in the nanopore sensor in response to translocation through the nanopore of at least one selected from the group consisting of DNA, RNA, nucleotides, nucleosides, oligonucleotides, proteins, polypeptides, and amino acids. ### Claim 34 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection develops a measurably distinct electrical signal indicative of an electrical potential local to at least one site in the nanopore sensor in response to translocation through the nanopore of a corresponding one of each of A, T, G, and C DNA bases. ### Claim 35 (depends on 34) The nanopore sensor of claim 34 wherein one of the two fluidic solution buffer concentrations is at least about 100 times greater than the other of the two fluidic solution buffer concentrations and wherein the electrical connection develops a distinct electrical signal indicative of an electrical potential local to at least one site in the nanopore sensor in response to translocation through the nanopore of a corresponding one of each of A, T, G, and C DNA bases, with a difference of at least about 5 mV between each distinct electrical signal. ### Claim 36 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection develops an electrical signal indicative of an electrical potential local to at least one site in the nanopore sensor in response to translocation through the nanopore of DNA fragments. ### Claim 37 (depends on 1) The nanopore sensor of claim 1 wherein the electrical connection develops an electrical signal that can be processed as a function of time to determine time of and duration of translocation of an object through the nanopore. ### Claim 38 A nanopore sensor comprising: a nanopore disposed in a support structure; a fluidic connection between a first fluidic reservoir and an inlet to the nanopore, with a first ionic solution of a first buffer concentration disposed in the first reservoir; a fluidic connection between a second fluidic reservoir and an outlet from the nanopore, with a second ionic solution of a second buffer concentration, different than the first concentration, disposed in the second reservoir, the nanopore providing the sole path of fluidic communication between the first and second reservoirs; and a transduction element, disposed at a location in the nanopore sensor, that develops a characteristic indicative of electrical potential local to at least one site in the nanopore sensor as an object translocates through the nanopore. ### Claim 39 (depends on 31) The nanopore sensor of claim 31 wherein the support structure comprises a lipid bilayer and wherein the transduction element comprises a region of the lipid bilayer that includes fluorescent dye which changes fluorescence in response to changes in local electrical potential. ### Claim 40 (depends on 30) The nanopore sensor of claim 30 wherein the support structure comprises a solid state material.