System and method for the acoustic loading of an analytical instrument using a continuous flow sampling probe

Patent metadata

Field	Value
Publication number	US-10770277-B2
Application number	US-201816198667-A
Country	US
Kind code	B2
Filing date	Nov 21, 2018
Priority date	Nov 22, 2017
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

A system and method are provided for loading a sample into an analytical instrument using acoustic droplet ejection (“ADE”) in combination with a continuous flow sampling probe. An acoustic droplet ejector is used to eject small droplets of a fluid sample containing an analyte into the sampling tip of a continuous flow sampling probe, where the acoustically ejected droplet combines with a continuous, circulating flow stream of solvent within the flow probe. Fluid circulation within the probe transports the sample through a sample transport capillary to an outlet that directs the analyte away from the probe to an analytical instrument, e.g., a device that detects the presence, concentration quantity, and/or identity of the analyte. When the analytical instrument is a mass spectrometer or other type of device requiring the analyte to be in ionized form, the exiting droplets pass through an ionization region, e.g., an electrospray ion source, prior to entering the mass spectrometer or other analytical instrument. The method employs active flow control and enables real-time kinetic measurements.

First claim

We claim:

1. An acoustic loading system for transporting an analyte in a fluid sample to an analytical instrument, comprising:
(a) a reservoir housing a fluid sample containing an analyte, the fluid sample having a fluid surface;
(b) an acoustic droplet ejector for generating acoustic radiation in a manner effective to eject a droplet of the fluid sample from the fluid surface; and
(c) a continuous flow sampling probe spaced apart from the fluid surface, comprising (i) a sampling tip for receiving the ejected droplet of the fluid sample, (ii) a solvent inlet for receiving a solvent from a solvent source, (iii) a solvent transport capillary for transporting the solvent from the solvent inlet to the sampling tip, where the ejected droplet combines with the solvent to form an analyte-solvent dilution, (iv) a sample outlet through which the analyte-solvent dilution is directed away from the sampling probe to an analytical instrument, and (v) a sample transport capillary for transporting the analyte-solvent dilution from the sampling tip to the sample outlet, wherein the sample transport capillary and the solvent transport capillary are in fluid communication at the sampling tip.

2. The system of claim 1 , wherein the continuous flow sampling probe comprises an outer capillary tube and an inner capillary tube co-axially disposed therein, the outer capillary tube and inner capillary tube defining the solvent transport capillary between the inner and outer capillary tubes and the inner capillary tube defining the sample transport capillary.

3. The system of claim 1 , wherein the acoustic droplet ejector comprises an acoustic radiation generator and a focusing means for focusing the acoustic radiation generated at a focal point near the surface of a fluid sample in the reservoir.

4. The system of claim 3 , wherein the acoustic droplet ejector is in acoustic coupling relationship with the reservoir.

5. The system of claim 1 , comprising a plurality of reservoirs each housing a fluid sample containing an analyte, wherein any one of the fluid samples may be the same or different as another of the fluid samples.

6. The system of claim 5 , further including a means for positioning the ejector in acoustic coupling relationship with respect to each of the reservoirs in succession.

7. The system of claim 5 , wherein the reservoirs are arranged in an array.

8. The system of claim 7 , wherein the reservoirs are contained within a substrate comprising an integrated multiple reservoir unit.

9. The system of claim 8 , further comprising a means for repositioning the reservoir unit relative to the acoustic ejector.

10. The system of claim 9 , wherein the fluid sample occupies a volume of no more than about 1 μL.

11. The system of claim 10 , wherein the fluid sample occupies a volume of about 10 pL to about 100 nL.

12. The system of claim 1 , wherein the acoustic droplet ejector is configured to eject a droplet having a volume of no more than about 3 nL.

13. The system of claim 12 , wherein the acoustic droplet ejector is configured to eject a droplet having a volume of no more than about 1 pL.

14. The system of claim 1 , further including a solvent pump operably connected to and in fluid communication with the solvent inlet for controlling solvent flow rate within the solvent transport capillary.

15. The system of claim 1 , further including a gas inlet through which a nebulizing gas flows from a gas source to the sample outlet, thereby aspirating the analyte-solvent dilution from the sample outlet.

16. The system of claim 15 , further including a gas pressure regulator operably connected to the gas inlet to control the nebulizing gas flow.

17. The system of claim 1 , further including an ionization source for ionizing analyte in the analyte-solvent dilution exiting the outlet.

18. The system of claim 17 , wherein the ionization source is an electrospray ion source.

19. The system of claim 18 , wherein the analytical instrument comprises a mass spectrometer.

20. The system of claim 1 , wherein the analytical instrument comprises a mass spectrometer.

21. The system of claim 1 , further including an adjuster adapted to move one of the inner capillary tube and the outer capillary tube longitudinally relative to the other.

22. A method for transporting a fluid sample containing an analyte to an analytical instrument, the method comprising:
(a) acoustically coupling an acoustic droplet ejector that generates acoustic radiation to a reservoir containing the fluid sample having a fluid surface;
(b) activating the acoustic ejector to generate acoustic radiation toward the reservoir and into the fluid sample in a manner effective to eject a droplet of the fluid sample from the fluid surface into a sampling tip of a continuous flow sampling probe, where the ejected droplet combines with a circulating solvent within the flow probe to form an analyte-solvent dilution, said sampling probe spaced apart from the fluid surface to provide a gap between the fluid surface and the sampling tip; and
(c) transporting the received fluid sample droplet in a solvent through a sample transport capillary within the sampling probe to a sample outlet, where the analyte-solvent dilution is directed away from the sampling probe to an analytical instrument.

23. The method of claim 22 , wherein the continuous flow sampling probe comprises a solvent inlet for receiving the solvent from a solvent source and a solvent transport capillary for transporting the solvent from the solvent inlet to the sampling tip.

24. The method of claim 23 , wherein the sample transport capillary and the solvent transport capillary are in fluid communication at the sampling tip.

25. The method of claim 24 , wherein the continuous flow sampling probe comprises a gas inlet.

26. The method of claim 25 , wherein step (c) comprises flowing a nebulizing gas from a gas source through a gas inlet to the sample outlet to aspirate the analyte-solvent dilution at the sample outlet.

27. The method of claim 26 , further comprising controlling sample flow rate within the sample transport capillary with a gas pressure regulator operably connected to the gas inlet.

28. The method of claim 27 , further comprising controlling solvent flow rate within the solvent transport capillary with a solvent pump operably connected to and in fluid communication with the solvent inlet.

29. The method of claim 28 , further comprising adjusting the solvent flow rate relative to the sample flow rate to provide a desired flow pattern at the sampling tip where the solvent transport capillary and the sample transport capillary are in fluid communication.

30. The method of claim 29 , wherein the desired flow pattern is a vortex.

31. The method of claim 30 , wherein the vortex is a supercritical vortex.

32. The method of claim 22 , wherein the reservoir is one of a plurality of reservoirs each housing a fluid sample containing an analyte, wherein the fluid samples in the reservoirs may be the same or different.

33. The method of claim 32 , wherein the reservoirs are arranged in an array.

34. The method of claim 33 , wherein the reservoirs are contained within a substrate comprising an integrated multiple reservoir unit.

35. The method of

Assignees

• Labcyte Inc
• Dh Technologies Dev Pte Ltd

Inventors

• DATWANI Sammy
• Arnold Don W
• Ghislain Lucien P
• Liu Chang
• Covey Thomas

Classifications

• H01J49/045

  with means for using a nebulising gas, i.e. pneumatically assisted · CPC title

• H01J49/0445

  with means for introducing as a spray, a jet or an aerosol (electrospray ion sources H01J49/165) · CPC title

• G01N29/222

  Constructional or flow details for analysing fluids (optoacoustic fluid cells G01N29/2425) · CPC title

• G01N29/02

  Analysing fluids (using acoustic emission techniques G01N29/14 {; constructional or flow details for analysing fluids G01N29/222; optoacoustic fluid cells G01N29/2425}) · CPC title

• B01L2400/0436

  acoustic forces, e.g. surface acoustic waves [SAW] · CPC title