Reaction monitoring

Patent metadata

Field	Value
Publication number	US-11309172-B2
Application number	US-201715672862-A
Country	US
Kind code	B2
Filing date	Aug 9, 2017
Priority date	Aug 9, 2016
Publication date	Apr 19, 2022
Grant date	Apr 19, 2022

Abstract

The invention generally relates to systems and methods for on-line reaction monitoring. In certain embodiments, the invention provides systems that include a reaction vessel having an outlet, a quantitation unit coupled to the outlet and configured to introduce internal standard and solvent into reaction solution flowed from the reaction vessel, one or more ion generating devices that receive flow from the quantitation unit, and a mass spectrometer. In certain embodiments, the invention provides systems for multiple reaction monitoring that include a plurality of reaction vessels, a plurality of ion generating devices, a plurality of channels, each channel coupling a reaction vessel to an ion generating device, an actuator coupled to the plurality of ion generating devices to thereby allow movement of the plurality of ion generating devices, and a mass spectrometer.

First claim

What is claimed is:

1. A reaction monitoring system, the system comprising:
a reaction vessel comprising an outlet;
a quantitation unit coupled to the outlet and configured to introduce internal standard and solvent into a reaction mixture flowed from the reaction vessel, wherein the quantitation unit comprises:
a first mixer in fluid communication with the outlet and an internal standard reservoir and operable to receive reaction mixture and internal standard respectively therefrom;
a second mixer in fluid communication with the first mixer and operable to receive mixed reaction mixture and internal standard therefrom;

a third mixer after the quantitation unit and in fluid communication with the second mixture, the third mixer comprising a first inlet that receives fluid flow from the second mixer, a second inlet that receives a spray solvent and an outlet;
one or more ion generating devices in fluid communication with the third mixer and operable to receive flow therefrom via one or more channels; and
a mass spectrometer that receives ions from the one or more ion generating devices.

2. The system according to claim 1 , wherein the mixer comprises a plurality of inlets and a union, wherein one of a plurality of inlets of the first mixer is coupled to the reaction vessel, another of the plurality of inlets of the first mixer is connected to the internal standard reservoir, and one or more outlets of the first mixer is coupled to the second mixer of the one or more mixers, which comprises one or more outlets that couple to the one or more ion generating devices.

3. The system according to claim 2 , wherein the second mixer comprises one or more outlets operably coupled to two ion generating devices.

4. The system according to claim 3 , wherein each ion generating device is configured for inductive charging electrospray ionization.

5. The system of claim 3 , wherein one of the two ion generating devices is in fluid communication with a solvent reservoir and operable to receive additional solvent to dilute, relative to the other ion generation device, the mixed reaction mixture and internal standard.

6. The system according to claim 1 , wherein the one or more ion generating devices are coupled to an actuator, the system further comprising:
one or more additional reaction vessels, each operably associated with an additional ion generating device coupled to the actuator,
wherein the actuator is configured to allow movement of the one or more ion generating devices and each additional ion generating device relative to the mass spectrometer.

7. The system of claim 1 , wherein the first mixer is in fluid communication with a solvent source and operable to receive solvent therefrom.

8. A system for quantifying multiple reactions, the system comprising:
a plurality of reaction vessels, each comprising an outlet;
a plurality of quantitation units each coupled to one of the outlets and configured to introduce internal standard and solvent into reaction solution flowed from one of the plurality of reaction vessels, wherein each of the plurality of quantitation units comprises a first mixer for receiving reaction solution, solvent, and internal standard and a second mixer for receiving the mixed reaction solution, solvent, and internal standard from the first mixer;
a plurality of third mixers, each coupled after each of the plurality of quantitation units to one of the outlets of the second mixers and in fluid communication with the second mixture of each of the plurality of quantitation units, each of the plurality of third mixers comprising a first inlet that receives fluid flow from the second mixer, a second inlet that receives a spray solvent and an outlet;
one or more ion generating devices for each of the plurality of quantitation units, the one or more ion generating devices each configured to receive flow from its associated third mixer of the plurality of third mixers via one or more channels connecting between each of the plurality of quantitation units and the one or more ion generating devices;
a mass spectrometer that receives ions from the one or more ion generating devices; and
an actuator coupled to the one or more ion generating devices for each of the plurality of quantitation units to thereby allow movement of the one or more ion generating devices for each of the plurality of quantitation units relative to the mass spectrometer.

9. The system according to claim 8 , wherein the one or more ion generating devices for each of the plurality of quantitation units are nano-electrospray ionization probes.

10. The system according to claim 9 , wherein the actuator comprises a rotary stage that holds each of the one or more ion generating devices for each of the plurality of quantitation units, and
wherein the actuator further comprises an electrode positioned proximate the rotary stage to impart an electric charge to each of the one or more ion generating devices for each of the plurality of quantitation units as the one or more ion generating devices for each of the plurality of quantitation units rotate past the electrode.

Assignees

• Purdue Research Foundation

Inventors

• Cooks Robert Graham
• Yan Xin
• Pulliam Christopher
• Bain Ryan M
• Flick Tawnya

Classifications

• H01J49/165 Primary

  Electrospray ionisation · CPC title

• G01N33/6848

  Methods of protein analysis involving mass spectrometry · CPC title

• H01J49/0409

  Sample holders or containers (containers for retaining a material to be analyzed, B01L3/50, for DNA, C12Q1/6834, for biological materials, G01N33/543) · CPC title

• H01J49/0031 Primary

  Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence) · CPC title