Purification of nucleic acids in a microfludic chip by separation

Patent metadata

Field	Value
Publication number	US-12357990-B2
Application number	US-201916964562-A
Country	US
Kind code	B2
Filing date	Jan 23, 2019
Priority date	Jan 24, 2018
Publication date	Jul 15, 2025
Grant date	Jul 15, 2025

Abstract

A system may include a horizontal actuator to move a tray, to which a microwell plate and a microfluidic chip may be coupled. The system may include a vertical actuator to move a support arm, to which a plurality of pipettes or pipette tips may be coupled. The system may include a rotational actuator to move an angle bracket, to which a magnet may be coupled. The system may include a heater, through which the pipettes may extend. The system may include a pump to control the flow of fluids through the pipettes.

First claim

The invention claimed is:

1. A method for removing one or more contaminants from a biological sample, the method comprising:
providing a first well and a second well connected to each other via a microchannel;
placing the biological sample into the first well;
introducing magnetic beads into the first well to attract target molecules within the biological sample;
applying an electric field across the microchannel, the electric field adapted to interact with at least some of the one or more contaminants and further adapted not to interact with the magnetic beads;
introducing a magnet generating a magnetic field into the vicinity of the first well, the magnetic field interacting with the magnetic beads; and
moving the magnetic beads into and through the microchannel and to the second well by moving the magnet,
wherein, while moving the magnetic beads into and through the microchannel and to the second well by moving the magnet, the electric field acts on at least some of the one or more contaminants to maintain at least some of the one or more contaminants in the microchannel as the magnetic beads and attracted target molecules move through the microchannel and to the second well,
wherein applying the electric field across the microchannel includes disposing a first probe in the first well and a second probe in the second well, the first probe and the second probe having opposite polarities, and
wherein moving the magnet includes rotating the magnet along an arcuate path.

2. The method of claim 1 , further comprising:
withdrawing the magnetic beads from the second well;
inserting the magnetic beads into a container including a fluid;
releasing the target molecules from the magnetic beads; and
removing the magnetic beads from the container.

3. The method of claim 1 , further comprising:
providing a third well and a second microchannel, the third well connected to the second well via the second microchannel;
moving the magnetic beads and target molecules through the second microchannel and to the third well using the magnet.

4. The method of claim 1 , further comprising:
providing a fluid in the first well, the second well, and the microchannel; and
creating a volume differential of the fluid between the second well and the first well such that a flow of the fluid is created in the microchannel from the second well toward the first well.

5. The method of claim 1 , further comprising:
stirring the biological sample in the first well; or
heating the biological sample in the first well.

6. A system for removing one or more contaminants from a biological sample, the system comprising:
magnetic beads that are tuned to attract target molecules from the biological sample;
a first well adapted to contain the biological sample and the magnetic beads;
a second well adapted to contain the biological sample and the magnetic beads;
a microchannel extending between the first well and the second well;
a magnet adapted to be moved into the vicinity of the first well, the magnet adapted to generate a magnetic field to interact with the magnetic beads, the magnet further capable of moving the magnetic beads from the first well to the second well via the microchannel;
an actuator coupled to the magnet, the actuator configured to rotate the magnet about a horizontal axis across an arcuate path of travel to move the magnetic beads from the first well to the second well via the microchannel;
a source of electrical power and two probes coupled thereto, the two probes adapted to apply an electric field across the microchannel when the source provides electrical power, such that
when the magnetic beads are moved by the magnet from the first well to the second well via the microchannel, the electric field interacts with at least some of the one or more contaminants to maintain at least some of the one or more contaminants in the microchannel as the magnetic beads and attracted target molecules move from the first well to the second well.

7. The system of claim 6 , further comprising:
a third well; and
a second microchannel, said third well connected to the second well via the second microchannel;
wherein the magnet is adapted to move along the second microchannel from the second well to the third well to move the magnetic beads and target molecules from the second well to the third well.

8. The system of claim 6 , further comprising:
a fluid in the first well, the second well, and the microchannel; and
a volume differential of the fluid between the second well and the first well, the volume differential adapted to provide a flow of the fluid in the microchannel from the second well toward the first well.

9. The system of claim 6 , further comprising a magnetic stirrer adapted to stir the contents of said first well.

10. The system of claim 6 , further comprising a heater adapted to heat said first well.

11. The system of claim 6 wherein a first one of the two probes is disposed in the first well and a second one of the two probes is disposed in the second well, the first probe and the second probe having opposite polarities.

12. The system of claim 6 , further comprising a third well in communication with the microchannel and a fourth well in communication with the microchannel, wherein a first one of the two probes is disposed in the third well and a second one of the two probes is disposed in the fourth well, the first probe and the second probe having opposite polarities, wherein the third well and the fourth well are on opposite sides of the microchannel and are offset from a center of the microchannel between the first well and the second well.

13. The system of claim 6 , wherein the arcuate path of travel includes a starting position, an intermediate position, and an ending position, and the actuator is further configured to:
rotate the magnet from the starting position in which the magnet is spaced by a first distance from the first well to the intermediate position in which the magnet is spaced by a second distance from the microchannel that is less than the first distance; and
rotate the magnet from the intermediate position to the ending position in which the magnet is spaced from the second well by the first distance.

14. A system for removing one or more contaminants from a biological sample, the system comprising:
magnetic beads that are tuned to attract target molecules from the biological sample;
a first well adapted to contain the biological sample and the magnetic beads;
a second well adapted to contain the biological sample and the magnetic beads;
a microchannel extending between the first well and the second well;
a third well in fluid communication with the microchannel;
a fourth well in fluid communication with the microchannel;
a magnet adapted to be moved into the vicinity of the first well, the magnet adapted to generate a magnetic field to interact with the magnetic beads, the magnet further capable of moving the magnetic beads from the first well to the second well via the microchannel; and
a first probe positioned in the third well and a second probe positioned in the fourth well, wherein the first and second probes have opposite polarities and are configured to apply an electric field across the microchannel via only the first probe and the second probe,
wherein when the magnetic beads are moved by the magnet from the first well to the second well via the microchannel, the electric field interacts with at least some of the one or more contaminants while not interacting with the magnetic beads to maintain at least some of the one or more contaminants in the microchannel as the m

Assignees

• Perkinelmer Health Sci Inc
• Revvity Health Sciences Inc

Inventors

• Troiano Derek

Classifications

• B03C2201/18

  Magnetic separation whereby the particles are suspended in a liquid · CPC title

• B03C1/023

  Separation using Lorentz force, i.e. deflection of electrically charged particles in a magnetic field · CPC title

• B03C1/01

  by addition of magnetic adjuvants · CPC title

• B01L2400/043

  magnetic forces · CPC title

• B01L2300/0816

  Cards, e.g. flat sample carriers usually with flow in two horizontal directions · CPC title