IP Library Granted Patent US 11,241,689
Granted Patent B2
US 11,241,689 · App. 15/670,896 · Granted Feb 8, 2022

Microchip electrophoresis inkjet dispensing

Inventors: Michael D. Furtaw (Lincoln, NE); Donald T. Lamb (Lincoln, NE)
Assignee: LI-COR, Inc.
B01L3/50273G01N27/44721G01N27/44739G01N27/44773G01N27/44791B01L2300/0681B01L2300/0829B01L2400/0421B01L2400/0478G01N27/44782
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Quick Facts
Patent No.
US 11,241,689
App. No.
15/670,896
Granted
Feb 8, 2022
Kind
B2
Abstract

Devices and methods are provided for the separation and dispensing of material using a microfluidic electrophoresis column, sheath liquid pump, and exit channel, all on the same monolithic chip. Material is separated in the electrophoresis column and passed into the exit chamber in response to a voltage potential between a first electrode within the electrophoresis column and a terminating electrode integrated into the chip. The terminating electrode can be in the sheath liquid pump chamber, the sheath liquid reservoir, or a separate flow channel that intersects the exit channel along with the electrophoresis column and sheath liquid pump chamber. The flow of sheath liquid into the exit chamber entrains separated analytes into an effluent that is dispensed out of the exit chamber via a discharge outlet.

Claims (50)

1. A microchip electrophoresis dispensing apparatus comprising:

an electrophoresis column having an input end and an output end, wherein the input end has an opening configured to accept a fluid sample;

a first electrode proximate to and in fluidic connection with the input end;

a terminating electrode in fluidic connection with the output end;

a sheath liquid reservoir;

a pump chamber connected to the sheath liquid reservoir;

an impulsive pump element configured to deform at least a portion of the pump chamber;

an exit channel having an upstream end connected to the pump chamber and a downstream end having a discharge outlet, wherein the output end of the electrophoresis column intersects the exit channel;

a surface positioned across a gap from the discharge outlet; and

a motor configured to move the surface or discharge outlet laterally with respect to one another,

wherein the surface is not electrically held at a voltage with respect to the first electrode or terminating electrode, and

wherein the impulsive pump element is configured to pump a sheath liquid from the sheath liquid reservoir to entrain analyte from the electrophoresis column and dispense the entrained analyte, as discrete droplets or a liquid stream, from the discharge outlet onto the surface.

2. The apparatus of claim 1 wherein the terminating electrode is within or upstream of the pump chamber.

3. The apparatus of claim 1 further comprising:

a flow channel, wherein the flow channel intersects the exit channel, and wherein the terminating electrode is within the flow channel.

4. The apparatus of claim 1 wherein the electrophoresis column, pump chamber, and exit channel are integrated on a single monolithic chip.

5. The apparatus of claim 1 wherein the surface supports a blotting membrane.

6. The apparatus of claim 1 further comprising:

a sieving matrix, wherein the sieving matrix is inside the electrophoresis column.

7. A method of dispensing one or more analytes from an electrophoresis column, the method comprising:

applying a voltage potential between an input end of an electrophoresis column and an output end of the electrophoresis column, wherein the voltage potential continues outside of the output end and into an exit channel, wherein the output end of the electrophoresis column intersects the exit channel, wherein the exit channel has an upstream end connect to a pump chamber and a downstream end having a discharge outlet, wherein the pump chamber is connected to a sheath liquid reservoir, and wherein the voltage is sufficient to electrophorese one or more analytes from the input end of the electrophoresis column to the output end of the electrophoresis column;

impulsively deforming the pump chamber, thereby pumping a sheath liquid from the sheath liquid reservoir to the exit channel;

entraining the one or more analytes in the sheath liquid to form an effluent;

dispensing the effluent through the discharge outlet of the exit channel;

contacting the dispensed effluent with a surface, positioned across a gap from the discharge outlet, wherein the surface is not held at a voltage with respect to the exit channel; and

moving the surface or discharge outlet relative to one another using a motor.

8. The method of claim 7 wherein the voltage potential continues outside of the output end of the electrophoresis column, through a portion of the exit channel, and into the pump chamber.

9. The method of claim 7 wherein the voltage potential continues outside of the output end of the electrophoresis column, through a portion of the exit channel, and into a flow channel, wherein the flow channel intersects the exit channel.

10. The method of claim 7 wherein the dispensing creates one or more droplets.

11. The method of claim 7 wherein the dispensing creates a liquid stream.

12. The method of claim 7 wherein the surface supports a blotting membrane.

13. The method of claim 10 , wherein the average volume of the one or more droplets is less than about one nanoliter.

14. A microchip electrophoresis dispensing apparatus comprising:

an electrophoresis column having an input end and an output end, wherein the input end has an opening configured to accept a fluid sample;

a first electrode proximate to and in fluidic connection with the input end;

a terminating electrode in fluidic connection with the output end;

a sheath liquid reservoir;

a pump chamber connected to the sheath liquid reservoir;

an impulsive pump element configured to deform at least a portion of the pump chamber;

an exit channel having an upstream end connected to the pump chamber and a downstream end having a discharge outlet, wherein the output end of the electrophoresis column intersects the exit channel;

a flat surface positioned across a gap from the discharge outlet, wherein the flat surface is positioned between 6 mm and 100 mm from the discharge outlet; and

a motor configured to move the surface or discharge outlet laterally with respect to one another,

wherein the impulsive pump element is configured to pump a sheath liquid from the sheath liquid reservoir to entrain analyte from the electrophoresis column and dispense the entrained analyte, as discrete droplets or a liquid stream, from the discharge outlet onto the flat surface.

15. The apparatus of claim 14 wherein the terminating electrode is within or upstream of the pump chamber.

16. The apparatus of claim 14 further comprising:

a flow channel, wherein the flow channel intersects the exit channel, and wherein the terminating electrode is within the flow channel.

17. The apparatus of claim 14 wherein the electrophoresis column, pump chamber, and exit channel are integrated on a single monolithic chip.

18. The apparatus of claim 1 , wherein the deforming of the pump chamber generates an acoustic wave.

19. The method of claim 7 , wherein the deforming of the pump chamber generates an acoustic wave.

20. The apparatus of claim 14 , wherein the deforming of the pump chamber generates an acoustic wave.

Assignments (6)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 6, 2023
From: LI-COR, INC.
To: LI-COR BIOTECH, LLC
Reel/Frame 065465/0085 →
SECURITY INTEREST Recorded Oct 30, 2023
From: LI-COR BIOTECH, LLC
To: MIDCAP FINANCIAL TRUST
Reel/Frame 065396/0454 →
CONFIRMATORY LICENSE Recorded Nov 4, 2022
From: LI-COR BIOSCIENCES, INC.
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 061883/0003 →
SECURITY INTEREST Recorded Dec 1, 2021
From: LI-COR, INC.
To: MIDCAP FINANCIAL TRUST
Reel/Frame 058293/0889 →
CONFIRMATORY LICENSE Recorded Feb 23, 2018
From: LI-COR BIOSCIENCES, INC.
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 045430/0357 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 15, 2017
From: FURTAW, MICHAEL D.; LAMB, DONALD T.
To: LI-COR, INC.
Reel/Frame 043300/0656 →
Continuity (2)
Provisional Application 62372244 · Aug 8, 2016
Related Publication 20180036729A1 · Feb 8, 2018