Detecting compounds in microfluidic droplets using mass spectrometry

Patent metadata

Field	Value
Publication number	US-10672601-B2
Application number	US-201716307698-A
Country	US
Kind code	B2
Filing date	Jun 6, 2017
Priority date	Jun 7, 2016
Publication date	Jun 2, 2020
Grant date	Jun 2, 2020

Abstract

Disclosed herein are devices and methods for detecting compounds in droplets using mass spectrometry. In some embodiments, the device comprises: a microfluidics-MS (microMS) device, wherein the microMS device comprises: a droplet-to-digital microfluidic device, wherein the droplet-to-digital microfluidic device comprises: a glass layer; an electrode layer comprising chrome electrodes etched onto one side of the glass layer; a dielectric layer configured for electrowetting; and a microfluidics layer comprising channels, pockets, and a droplet generator, for example a T-junction droplet generator, wherein the pockets are connected to the channels; and a mass spectrometry plate, wherein the mass spectrometry plate is reversibly sealed to the microfluidic device.

First claim

What is claimed is:

1. A device for detecting compounds in microfluidic droplets using mass spectrometry, comprising:
a microfluidic device comprising a droplet-to-digital microfluidic device, wherein the droplet-to-digital microfluidic device comprises:
a glass layer;
an electrode layer;
a dielectric layer; and
a microfluidics layer; and
a nanostructure-initiator mass spectrometry plate, wherein the nanostructure-initiator mass spectrometry plate is reversibly sealed to the microfluidic device.

2. The device of claim 1 ,
wherein the glass layer is on a first side of the electrode layer,
wherein the dielectric layer is on a second side of the electrode layer, wherein the electrode layer is on a first side of the dielectric layer,
wherein the microfluidics layer is on a second side of the dielectric layer, wherein the dielectric layer is on a first side of the microfluidics layer, and
wherein the nanostructure-initiator mass spectrometry plate is on a second side of the microfluidics layer.

3. The device of claim 2 , wherein the electrode layer comprises electrodes etched onto one side of the glass layer.

4. The device of claim 3 , wherein the electrodes comprise chrome electrodes.

5. The device of claim 1 , wherein the electrode layer is configured to manipulate droplets in the microfluidics layer, and wherein the dielectric layer is configured for electrowetting.

6. The device of claim 1 , wherein the glass layer comprises fluidic access ports.

7. The device of claim 1 , wherein the microfluidics layer comprises channels, wherein depths of some of the channels are about 5-250 μm, and wherein widths of some of the channels are 5-500 μm.

8. The device of claim 7 , wherein the microfluidics layer comprises a droplet generator, wherein the droplet generator is connected to the channels.

9. The device of claim 8 , wherein the droplet generator comprises a T-junction droplet generator.

10. The device of claim 7 , wherein the microfluidics layer comprises pockets connected to the channels of the microfluidics layer.

11. The device of claim 1 , wherein the nanostructure-initiator mass spectrometry plate is reversibly sealed to the microfluidic device with a rubbery seal at 1.5-9 MPa.

12. The device of claim 1 , wherein the nanostructure-initiator mass spectrometry plate is reversibly sealed at a pressure higher than an inner pressure of the microfluidics device.

13. A method for detecting compounds in droplets using mass spectrometry, comprising:
providing a microfluidics-mass spectrometry (microMS) device, comprising:
a droplet-to-digital microfluidic device, wherein the droplet-to-digital microfluidic device comprises:
a glass layer, wherein the glass layer comprises fluidic access ports;
an electrode layer, wherein the electrode layer comprises chrome electrodes etched onto one side of the glass layer;
a dielectric layer, wherein the dielectric layer is configured for electrowetting; and
a microfluidics layer, wherein the microfluidics layer comprises channels, pockets, and a droplet generator, wherein the pockets are connected to the channels;
a nanostructure-initiator mass spectrometry plate, wherein the nanostructure-initiator mass spectrometry plate is reversibly sealed to the microfluidic device; and
producing droplets comprising one or more compounds using the droplet generator of the microMS device; and
generating mass spectra for the droplets to detect one or more compounds in the droplets.

14. The method of claim 13 ,
wherein the glass layer is on a first side of the electrode layer,
wherein the dielectric layer is on a second side of the electrode layer, wherein the electrode layer is on a first side of the dielectric layer,
wherein the microfluidics layer is on a second side of the dielectric layer, wherein the dielectric layer is on a first side of the microfluidics layer, and
wherein the nanostructure-initiator mass spectrometry plate is on a second side of the microfluidics layer.

15. The method of claim 13 , further comprising manipulating the droplets generated using the electrode layer, wherein manipulating the droplets using the electrode layer comprises splitting at least one of the droplets, mixing at least two of the droplets, moving at least one of the droplets, or a combination thereof.

16. The method of claim 13 , wherein the nanostructure-initiator mass spectrometry plate comprises micropatterns, the method further comprising:
aligning the nanostructure-initiator mass spectrometry plate with the microfluidics device to allow targeted droplet deposition using the micropatterns.

17. The method of claim 13 , wherein the nanostructure-initiator mass spectrometry plate comprises at least 640 mass spectrometry pads, and wherein the microfluidics layer comprises at least 640 pockets.

18. The method of claim 17 , further comprising depositing the droplets into the pockets, wherein the volume of at least one of the one or more mixtures is about 1 microliter, about 1 nanoliter, or about 1 picoliter.

19. The method of claim 17 , further comprising manipulating the droplets from the pockets into the mass spectrometry pads.

Assignees

• Univ California

Inventors

• Northen Trent Russell
• Heinemann Joshua Vance

Classifications

• H01J49/26

  Mass spectrometers or separator tubes · CPC title

• B01L2200/0689

  Sealing · CPC title

• B01L2300/0816

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

• B01L2300/0887

  Laminated structure · CPC title

• H01J49/164

  Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI] (sample holders H01J49/0418) · CPC title