Nanopore sensor devices

Patent metadata

Field	Value
Publication number	US-2024377380-A1
Application number	US-202218553192-A
Country	US
Kind code	A1
Filing date	Mar 1, 2022
Priority date	Mar 31, 2021
Publication date	Nov 14, 2024
Grant date	—

Abstract

An example of a nanopore sensor device includes one or more cis wells; a cis electrode; a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid/solid-state membrane having a nanopore; a plurality of trans electrodes, each of the plurality of trans electrodes associated with one of the plurality of trans wells; a first concentration of an electrolyte within the one or more cis wells; and a second concentration of the electrolyte within the trans wells, wherein the first concentration is higher than the second concentration.

First claim

What is claimed is:

1 . A nanopore sensor device, comprising:
one or more cis wells; a cis electrode; a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid/polymer/solid-state membrane having a nanopore; a plurality of trans electrodes, each of the plurality of trans electrodes associated with one of the plurality of trans wells; a first concentration of an electrolyte within the one or more cis wells; and a second concentration of the electrolyte within the trans wells, wherein the first concentration is higher than the second concentration.

2 . The nanopore sensor device as defined in claim 1 , further comprising:
a stimulus source coupled to each of the plurality of trans electrodes either individually or via multiplexing, wherein the stimulus source is to cause current to flow through the nanopore; and a controller coupled to the stimulus source, the controller configured to individually/selectively address the plurality of trans electrodes to cause an ionic current through the nanopore of an addressed trans electrode of the plurality of trans wells.

3 . The nanopore sensor device as defined in claim 2 , wherein the ionic current comprises an amount of anions of the electrolyte translocating through the nanopore to the addressed trans well that is higher than an amount of cations of the electrolyte translocating through the nanopore from the addressed trans well.

4 . The nanopore sensor device as defined in claim 2 , wherein the controller is further configured to cause the stimulus source to apply a unipolar electric current between the cis electrode and the addressed trans electrode of the addressed trans well of the plurality of trans wells.

5 . The nanopore sensor device as defined in claim 1 , wherein the nanopore has a plurality of positively charged residues on an inner surface of the nanopore.

6 . The nanopore sensor device as defined in claim 5 , wherein the plurality of positively charged residues on the inner surface are located at a constriction zone of the nanopore.

7 . The nanopore sensor device as defined in claim 1 , wherein a ratio of the first concentration to the second concentration ranges from about 10:1 to about 3:1.

8 . A nanopore sensor kit, comprising:
a nanopore sensor device, including:
one or more cis wells including a fluid inlet;
a cis electrode;
a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid/polymer/solid-state membrane having a nanopore;
a plurality of trans electrodes, each of the plurality of trans electrodes associated with one of the plurality of trans wells; and
a first concentration of an electrolyte within the one or more cis wells and the plurality of trans well; and
a second concentration of the electrolyte to be introduced into the one or more cis wells through the fluid inlet such that the one or more cis wells contain the second concentration of the electrolyte and the plurality of trans wells contain the first concentration of the electrolyte at an initial cycle of the nanopore sensor device, wherein the second concentration is higher than the first concentration.

9 . A method of detecting an ionic current to analyze a biological compound, comprising:
providing a nanopore within a membrane separating a cis well and a trans well, the nanopore having a plurality of positively charged residues on an inner surface; providing an electrolyte within the cis well and the trans well; and applying an electric current between a cis cathode at least partially exposed to the cis well and a trans anode at least partially exposed to the trans well to generate an ionic current through the nanopore, wherein the plurality of positively charged residues of the nanopore inhibits translocation of cations from the trans well to the cis well during application of the electric current.

10 . The method as defined in claim 9 , wherein the plurality of positively charged residues on the inner surface are located at a constriction zone of the nanopore.

11 . The method as defined in claim 9 , wherein the nanopore is a modified protein with negatively charged residues, neutral charged resides, or both negatively charged residues and neutral charged resides mutated to the positively charged residues.

12 . The method as defined in claim 9 , wherein the nanopore is a solid-state nanopore with organic positively charged species, inorganic positively charged species, or both organic positively charged species and inorganic positively charged species as the positively charged residues.

13 . The method as defined in claim 9 , wherein the applied electric current is a unipolar current.

14 . The method as defined in claim 9 , wherein the cis well comprises a higher concentration of the electrolyte than the trans well during application of the electric current.

15 . The method as defined in claim 9 , wherein one of:
the electrolyte is a redox couple having a negative charge and is incorporated into a redox-inactive buffer that includes an anion having a diameter greater than a diameter of a constriction zone of the nanopore; and the electrolyte is a redox couple having a positive charge and is incorporated into a redox-inactive buffer that includes a cation having a diameter greater than a diameter of a constriction zone of the nanopore.

16 . A nanopore sensor device, comprising:
one or more cis wells; a cis electrode; a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid/polymer/solid-state membrane having a nanopore; a plurality of trans electrodes, each of the plurality of trans electrodes associated with one of the plurality of trans wells; an electrolyte solution including:
a redox-inactive buffer that includes a redox inactive species having a diameter greater than a diameter of a constriction zone of the nanopore; and
a redox couple.

17 . The nanopore sensor device as defined in claim 16 , further comprising:
a stimulus source coupled to each of the plurality of trans electrodes either individually or via multiplexing, wherein the stimulus source is to cause current to flow through the nanopore; and a controller coupled to the stimulus source, the controller configured to individually/selectively address the plurality of trans electrodes to cause an ionic current through the nanopore of an addressed trans electrode of the plurality of trans wells.

18 . The nanopore sensor device as defined in claim 17 , wherein the ionic current comprises an amount of the redox couple translocating through the nanopore to the addressed trans electrode without an amount of the redox-inactive species.

19 . The nanopore sensor device as defined in claim 17 , wherein the controller is further configured to apply a unipolar electric current between the cis electrode and the addressed trans electrode of the addressed trans well of the plurality of trans wells.

20 . The nanopore sensor device as defined in claim 16 , wherein the nanopore has a plurality of positively charged residues on an inner surface of the nanopore.

21 . A nanopore sensor device, comprising:
one or more cis wells; a cis electrode; a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid/polymer/solid-state membrane having a nanopores with a plurality of positively charged residues on an inner surfac

Assignees

• Illumina Inc

Inventors

• Boyanov Boyan
• Mandell Jeffrey G
• Mcdonald Seth M

Classifications

• C12Q1/6869 Primary

  Methods for sequencing · CPC title

• B82B3/0038

  Manufacturing processes for forming specific nanostructures not provided for in groups B82B3/0014 - B82B3/0033 · CPC title

• B82B1/008

  Nanostructures not provided for in groups B82B1/001 - B82B1/007 · CPC title

• C12Q2565/631

  being a biochannel or pore · CPC title

• C12Q2563/137

  Metal/ion, e.g. metal label · CPC title