Plasmon resonance (PR) system, instrument, cartridge, and methods and configurations thereof

Patent metadata

Field	Value
Publication number	US-11278890-B2
Application number	US-201917265162-A
Country	US
Kind code	B2
Filing date	Aug 6, 2019
Priority date	Aug 6, 2018
Publication date	Mar 22, 2022
Grant date	Mar 22, 2022

Abstract

A plasmon resonance system, instrument, cartridge, and methods for analysis of analytes is disclosed. A PR system is provided that may include a DMF-LSPR cartridge that may support both digital microfluidic (DMF) capability and localized surface plasmon resonance (LSPR) capability for analysis of analytes. In some examples, the DMF portion of the DMF-LSPR cartridge may include an electrode arrangement for performing droplet operations, whereas the LSPR portion of the DMF-LSPR cartridge may include an LSPR sensor. In other examples, the LSPR portion of the DMF-LSPR cartridge may include an in-line reference channel, wherein the in-line reference channel may be a fluid channel including at least one functionalized LSPR sensor (or sample spot) and at least one non-functionalized LSPR sensor (or reference spot). Additionally, methods of using the PR system for analysis of analytes are provided.

First claim

What is claimed is:

1. A cartridge for use with an instrument, comprising:
a digital microfluidics (DMF) portion comprising at least one electrode to perform fluid operations on a fluid in the DMF portion;
an analog fluid portion comprising at least one fluid channel, wherein the at least one fluid channel is fluidly coupled with the DMF portion for receipt of a fluid from the DMF portion to provide a continuous flow of the fluid in the at least one fluid channel; and
a sensor located in the at least one fluid channel, wherein the analog fluid portion is configured to flow the fluid provided in the at least one fluid channel into contact with the sensor for real-time measurement of the fluid by the sensor.

2. The cartridge of claim 1 wherein the analog fluid portion is configured to flow the fluid provided in the at least one fluid channel across the surface of the sensor for real-time measurement of the fluid by the sensor.

3. The cartridge of claim 1 , wherein the sensor is located on a surface of the at least one fluid channel.

4. The cartridge of claim 1 , wherein the at least one fluid channel comprises an enlarged region for accommodating a sensor and the sensor is located on a surface of the enlarged region.

5. The cartridge of claim 4 wherein the enlarged region is substantially ovular or circular disk-shaped.

6. The cartridge of claim 1 , wherein the fluid comprises a liquid reagent, buffer solution, or liquid sample.

7. The cartridge of claim 1 , wherein the sensor comprises a surface plasmon resonance (SPR) sensor for real-time measurement of an optical signal of the SPR sensor in response to the continuous flow of the fluid in the at least one fluid channel.

8. The cartridge of claim 7 , wherein the fluid is present in the cartridge and comprises an analyte fluid comprising an analyte and is flowing in the continuous flow portion at the SPR sensor establishing a mass transport rate of the analyte that is higher than a binding rate of the analyte fluid at the SPR sensor.

9. The cartridge of claim 8 wherein the fluid is flowing in the continuous flow portion at a flow rate not less than about 25 nl/min and not greater than about 10,000 μl/min.

10. The cartridge of claim 7 , further comprising:
a reservoir electrode in the DMF portion to receive and maintain the fluid in the DMF portion; and
a plurality of droplet operation electrodes in the DMF portion that are operative to supply the fluid from the reservoir electrode to the at least one fluid channel of the analog fluid portion.

11. The cartridge of claim 7 , further comprising:
a plurality of reservoir electrodes in the DMF portion each maintaining a different fluid; and
wherein the at least one electrode is disposed relative to the plurality of reservoir electrodes to perform mixing of the different fluids prior to providing the fluid to the at least one fluid channel of the analog fluid portion.

12. The cartridge of claim 7 , further comprising at least one boundary electrode disposed at a boundary between the DMF portion and the analog fluid portion wherein the boundary electrode is disposed relative to the at least one fluid channel to allow a fluid droplet at the boundary electrode to enter the at least one fluid channel.

13. The cartridge of claim 12 wherein the boundary electrode is disposed at, but does not span, the boundary between the DMF portion and the analog fluid portion.

14. The cartridge of claim 12 wherein the boundary electrode overlaps the boundary between the DMF portion and the analog fluid portion.

15. The cartridge of claim 7 , further comprising an electrical contact in electrical communication with the electrode wherein the electrical contact is configured for interface with a controller for control of the at least one electrode.

16. The cartridge of claim 7 , wherein the at least one electrode is configured to perform the fluid operation by electrowetting.

17. The cartridge of claim 7 , further comprising:
a feedback sensor operative to detect droplet operation of the DMF portion, the feedback sensor being operable to communicate with the controller to provide feedback regarding the droplet operation such that the controller may control the at least one electrode to supply droplets as needed to prevent introduction of filler media from the DMF portion into the the at least one fluid channel of the analog fluid portion.

18. The cartridge of claim 17 wherein the feedback sensor comprises at least one of a capacitive or an optical sensor, and optionally wherein a transition electrode doubles as an element of the sensor.

19. The cartridge of claim 17 , wherein the feedback sensor is operative to measure a droplet position, velocity, and volume of a droplet in the DMF portion.

20. The cartridge of claim 7 , wherein the SPR sensor comprises a sensor surface comprising one of nanosized structures distributed on the sensor surface or a continuous film comprising nano-sized features.

21. The cartridge of claim 7 , wherein the sensor surface of the SPR sensor is functionalized with a specific capture molecule to which a target molecule of an analyte fluid binds to change the optical signal of the SPR sensor.

22. The cartridge of claim 21 wherein the capture molecule comprises a ligand immobilized on the surface of the sensor that is sensitive to binding with the target molecule of the analyte fluid to change optical properties of the surface of the sensor resulting in the change of the optical signal of the SPR sensor.

23. The cartridge of claim 22 wherein the change of the optical properties comprises a change in the optical signal resulting from light interacting with the sensor surface.

24. The cartridge of claim 7 , wherein the optical signal is detected within about 1000 nm from the sensor surface.

25. The cartridge of any claim 7 , wherein the optical signal is detected within about 100 nm from the sensor surface.

26. The cartridge of claim 7 , wherein the SPR portion is substantially transparent to an illumination source incident on the SPR sensor on at least one side of the SPR sensor to facilitate real-time optical measurement of the SPR sensor in a reflectance mode.

27. The cartridge of claim 7 , wherein the SPR portion is substantially transparent to an illumination source incident on the SPR sensor on opposite sides of the SPR sensor to facilitate real-time optical measurement of the SPR sensor in a transmission mode.

28. The cartridge of claim 7 , wherein the cartridge is a multiple-channel cartridge comprising:
a plurality of fluid channels; and
a plurality of droplet operations electrodes disposed relative to the plurality of fluid channels that are operative to supply a continuous fluid flow of fluid to the plurality of fluid channels.

29. The cartridge of claim 7 , further comprising:
a fluid inlet at a boundary of the DMF portion and the analog fluid portion in fluid communication with the at least one fluid channel; and
a fluid outlet in fluid communication with the at least one fluid channel and operable to engage with a flow mechanism to establish the continuous fluid flow in the at least one fluid channel between the fluid inlet and the fluid outlet;
wherein the fluid comprises an analyte fluid; and
wherein the SPR sensor is operable to detect analyte affinity of the analyte fluid from the continuous fluid flow in the

Assignees

• Nat Res Council Canada

Inventors

• Denomme Ryan
• Malic Lidija
• Brassard Daniel
• Morton Keith
• Veres Teodor

Classifications

• G01N21/554 Primary

  detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance · CPC title

• G01N2201/061

  Sources · CPC title

• G01N2201/023

  Controlling conditions in casing · CPC title

• B01L2300/0645

  Electrodes · CPC title

• B01L3/502784

  specially adapted for droplet or plug flow, e.g. digital microfluidics · CPC title