Device for the analysis of nucleic acid molecules

Patent metadata

Field	Value
Publication number	US-12478964-B2
Application number	US-202117186954-A
Country	US
Kind code	B2
Filing date	Feb 26, 2021
Priority date	May 7, 2015
Publication date	Nov 25, 2025
Grant date	Nov 25, 2025

Abstract

The invention proposes a device for analyzing nucleic acid molecules (M), comprising: —a bead ( 20 ), on which one molecule can be anchored at one end, —a surface ( 520 ), on which the molecule can be anchored at the other end, —an actuator ( 30 ), adapted to cause the bead to move relative to said surface in one direction, —a sensor ( 50 ), adapted to measure a distance between the bead and the surface, the device further comprising a well ( 11 ), having an axis (X-X) extending along the direction of motion of the bead and a bottom ( 110 ) formed by said surface, said well being filled with electrically conductive solution ( 40 ), and receiving the bead, the sensor being adapted to measure an impedance of the well, depending on a distance between the bead and the surface, to determine, the distance between the bead and the surface.

First claim

The invention claimed is:

1 . A device, comprising:
a plate having a top surface and a bottom surface, the plate comprising a well formed therein, the well extending along an axis into the plate from the top surface to a base of the well, the base being defined by the plate, the well opening at the top surface, the axis being normal to the bottom surface and the base of the well closing the well at the bottom surface; a nucleic acid molecule disposed in the well, the nucleic acid molecule comprising a first end, the first end being anchored to a surface at or proximate to the base; a bead disposed in the well, the nucleic acid molecule comprising a second end, the bead being anchored to the second end, an actuator configured to cause the bead to move relative to the bottom surface along the axis within a portion of the well along the axis, the portion of the well having a cross-sectional area measured perpendicular to the axis, the cross-section area increasing as a distance from the base to the cross-section area increases; and a sensor configured to measure an impedance of the well, the impedance depending on a distance between the bead and the base.

2 . The device of claim 1 , further comprising an electrically conductive solution disposed in the well.

3 . The device of claim 1 , wherein the sensor comprises:
a main electrode positioned over the top surface of the plate; a secondary electrode positioned over the bottom surface of the plate; and an electronic circuit configured to measure a current flow between the main electrode and the secondary electrode.

4 . The device of claim 1 , wherein the plate comprises an electrically insulating material.

5 . The device of claim 1 , wherein a minimum cross-sectional area of the portion of the well along which the bead is movable is greater than a diameter of the bead.

6 . The device of claim 1 , wherein the cross-sectional area of the well measured at the base of the well is greater than a diameter of the bead.

7 . The device of claim 1 , wherein the bead has a diameter in a range from 1 μm to 5 μm.

8 . The device of claim 1 , wherein the cross-sectional area of the portion of the well along which the bead is movable increases linearly as the distance from the base of the well increases.

9 . The device of claim 1 , wherein the bead comprises a paramagnetic material.

10 . The device of claim 1 , wherein:
the plate comprises a plurality of wells formed therein, each respective well of the plurality of wells extending into the plate from the top surface along an axial normal to the bottom surface; a nucleic acid molecule is disposed in each respective well of the plurality of wells and anchored at a first end to a surface at or proximate to a base of the respective well; and a bead is disposed in each respective well of the plurality of wells, the bead is anchored to the nucleic acid molecule at a second end of the nucleic acid molecule of the respective well.

11 . The device of claim 10 , wherein the actuator comprises at least one magnet displaceably disposed over the top surface of the plate, the at least one magnet configured to be displaced along an axis parallel to the axis of the well.

12 . The device of claim 11 , wherein the actuator further comprises a plurality of bars fixedly disposed over the top surface of the plate, each bar of the plurality of bars extending between two adjacent wells of the plurality of wells such that a pair of bars of the plurality of bars is associated with each well and are disposed on opposing sides of the respective wells, the plurality of bars comprising a magnetic material, the plurality of bars configured to be magnetized under the influence of the magnetic field produced by the magnet.

13 . The device of claim 1 , wherein:
the bead is further configured to be movable within the well along the axis of the well, the well having a cross-sectional area measured perpendicular to the axis that increases between the base of the well defined by the plate and the top surface of the plate.

14 . The device of claim 13 , wherein the actuator comprises at least one magnet displaceably disposed over the top surface of the plate, the at least one magnet configured to be displaced along an axis parallel to the axis of the well.

15 . The device of claim 14 , wherein the actuator further comprises a pair of bars fixedly disposed over the top surface of the plate and on opposing sides of the well, the pair of bars comprising a magnetic material, the pair of bars configured to be magnetized under the influence of the magnetic field produced by the at least one magnet.

16 . The device of claim 13 , wherein the sensor comprises:
a main electrode disposed over the top surface of the plate; a secondary electrode disposed over the bottom surface of the plate; and an electronic circuit configured to measure a current flow between the main electrode and the secondary electrode.

17 . The device of claim 13 , wherein the plate comprises an electrically insulating material.

18 . The device of claim 13 , wherein the bead comprises a paramagnetic material.

Assignees

• Paris Sciences Et Lettres—Quartier Latin
• Centre Nat Rech Scient
• Univ Paris Diderot Paris 7
• Univ Sorbonne
• Paris Sciences Et Lettres
• Univ Paris Cite

Inventors

• Croquette Vincent
• Bensimon David
• Ouellet Jimmy
• Allemand Jean-François
• Andre Charles
• Hamilton Gordon

Classifications

• G01N27/3275

  Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction · CPC title

• G01N27/07

  Construction of measuring vessels; Electrodes therefor · CPC title

• C12Q2563/155

  Particles of a defined size, e.g. nanoparticles · CPC title

• C12Q2563/116

  electrical properties of nucleic acids, e.g. impedance, conductivity or resistance · CPC title

• C12Q2525/301

  Hairpin oligonucleotides · CPC title