# US 2021/0242005 A1 · Inline chemical agent addition for inline reaction with fluid sample for analytic determinations

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- Number: US 2021/0242005 A1
- Document ID: US20210242005A1
- Status: Published application
- Kind: A1
- Application number: 17/166,757
- Filed: 2021-02-03
- Published: 2021-08-05
- Earliest claimed: 2020-02-03
- Assignees: Elemental Scientific, Inc.
- Applicants: Elemental Scientific, Inc.
- Inventors: Charles D. Quarles, JR.
- Web page: https://patentgrep.com/patent/US20210242005A1

## CPC

- H01J 49/0413: {for automated handling}
- H01J 49/0431: {for liquid samples (interfaces to liquid chromatographs G01N30/7233)}
- B01L 3/502: {with fluid transport, e.g. in multi-compartment structures}
- B01L 3/567: {Valves, taps or stop-cocks}
- G01N 30/72: Mass spectrometers {(mass spectrometers per se H01J49/00)}
- H01J 49/105: {using high-frequency excitation, e.g. microwave excitation, Inductively Coupled Plasma [ICP]}
- H01J 49/165: {Electrospray ionisation}
- B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
- B01L 2200/16: Reagents, handling or storing thereof
- B01L 2300/049: Valves integrated in closure
- H01J 49/26: Mass spectrometers or separator tubes
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Systems and methods for controlled, inline introduction of chemical agents to an inline fluid sample are described. A method embodiment includes, but is not limited to, receiving a fluid sample with a valve; receiving a chemical agent with the valve; introducing the fluid sample and the chemical agent inline via a mixing port of the valve to produce a mixed sample; transferring the mixed sample to a second valve; directing the mixed sample to a sample holding loop fluidically coupled with the second valve; holding the mixed sample within the sample holding loop for a holding period of time to permit a reaction between the fluid sample and the chemical agent; and directing the mixed sample from the sample holding loop to an analytic instrument following expiration of the holding period of time.

## Claims

### Claim 1

A method comprising:
receiving a fluid sample from an autosampler with a valve system;
receiving a chemical agent with the valve system;
introducing, via a pump system, the fluid sample and the chemical agent inline via a mixing port of the valve system to produce a mixed sample;
transferring, via the pump system, the mixed sample to a sample holding loop fluidically coupled with the valve system;
holding the mixed sample within the sample holding loop for a holding period of time to permit a reaction between the fluid sample and the chemical agent; and
directing, via the pump system, the mixed sample from the sample holding loop to an analytic instrument following expiration of the holding period of time.

### Claim 2 (depends on 1)

The method of claim 1, wherein directing, via the pump system, the mixed sample from the sample holding loop to an analytic instrument following expiration of the holding period of time includes:
directing, via the pump system, the mixed sample from the sample holding loop through a separation column to separate one or more chemical species from respective other chemical species in the mixed sample and subsequently to the analytic instrument following expiration of the holding period of time.

### Claim 3 (depends on 1)

The method of claim 1, wherein the chemical agent is introduced to the valve system through action of at least one pump.

### Claim 4 (depends on 1)

The method of claim 1, wherein the chemical agent includes a chiral derivatization agent.

### Claim 5 (depends on 1)

The method of claim 1, further comprising:
subsequent to directing the mixed sample from the sample holding loop to the analytic instrument following expiration of the holding period of time, receiving a second fluid sample from the autosampler with the valve system;
introducing the second fluid sample and the chemical agent inline via the mixing port of the valve system to produce a second mixed sample; and
holding the second mixed sample within the sample holding loop for a second holding period of time to permit a reaction between the second fluid sample and the chemical agent, wherein the second holding period of time differs from the first holding period of time.

### Claim 6 (depends on 5)

The method of claim 5, further comprising:
directing the second mixed sample from the sample holding loop to the analytic instrument following expiration of the second holding period of time.

### Claim 7 (depends on 6)

The method of claim 6, further comprising:
subsequent to directing the second mixed sample from the sample holding loop to the analytic instrument following expiration of the second holding period of time, receiving a third fluid sample from the autosampler with the valve system;
introducing the third fluid sample and the chemical agent inline via the mixing port of the valve system to produce a third mixed sample; and
holding the third mixed sample within the sample holding loop for a third holding period of time to permit a reaction between the third fluid sample and the chemical agent, wherein the third holding period of time differs from each of the first holding period of time and the second holding period of time.

### Claim 7 (depends on 7)

The method of claim 7, further comprising:
directing the third mixed sample from the sample holding loop to the analytic instrument following expiration of the third holding period of time.

### Claim 9 (depends on 1)

The method of claim 1, wherein the analytic instrument includes a mass spectrometer.

### Claim 10 (depends on 9)

The method of claim 9, wherein the mass spectrometer includes an electrospray ionization mass spectrometer.

### Claim 11

A method comprising:
receiving a fluid sample with a first valve;
receiving a chemical agent with the first valve;
introducing, via a pump system, the fluid sample and the chemical agent inline via a mixing port of the first valve to produce a mixed sample;
transferring, via the pump system, the mixed sample to a second valve;
directing the mixed sample to a sample holding loop fluidically coupled with the second valve;
holding the mixed sample within the sample holding loop for a holding period of time to permit a reaction between the fluid sample and the chemical agent; and
directing, via the pump system, the mixed sample from the sample holding loop to an analytic instrument following expiration of the holding period of time.

### Claim 12 (depends on 11)

The method of claim 11, wherein directing, via the pump system, the mixed sample from the sample holding loop to an analytic instrument following expiration of the holding period of time includes:
directing, via the pump system, the mixed sample from the sample holding loop through a separation column to separate one or more chemical species from respective other chemical species in the mixed sample and subsequently to the analytic instrument following expiration of the holding period of time.

### Claim 13 (depends on 11)

The method of claim 11, wherein the chemical agent is introduced to the valve system through action of at least one pump.

### Claim 14 (depends on 11)

The method of claim 11, wherein the chemical agent includes a chiral derivatization agent.

### Claim 15 (depends on 11)

The method of claim 11, further comprising:
subsequent to directing the mixed sample from the sample holding loop to the analytic instrument following expiration of the holding period of time, receiving a second fluid sample with the first valve;
introducing the second fluid sample and the chemical agent inline via the mixing port of the first valve to produce a second mixed sample;
transferring the second mixed sample to the second valve;
directing the second mixed sample to the sample holding loop; and
holding the second mixed sample within the sample holding loop for a second holding period of time to permit a reaction between the second fluid sample and the chemical agent, wherein the second holding period of time differs from the first holding period of time.

### Claim 16 (depends on 15)

The method of claim 15, further comprising:
directing the second mixed sample from the sample holding loop to the analytic instrument following expiration of the second holding period of time.

### Claim 17 (depends on 16)

The method of claim 16, further comprising:
subsequent to directing the second mixed sample from the sample holding loop to the analytic instrument following expiration of the second holding period of time, receiving a third fluid sample with the first valve;
introducing the third fluid sample and the chemical agent inline via the mixing port of the first valve to produce a third mixed sample;
transferring the third mixed sample to the second valve;
directing the third mixed sample to the sample holding loop; and
holding the third mixed sample within the sample holding loop for a third holding period of time to permit a reaction between the third fluid sample and the chemical agent, wherein the third holding period of time differs from each of the first holding period of time and the third holding period of time.

### Claim 18 (depends on 17)

The method of claim 17, further comprising:
directing the third mixed sample from the sample holding loop to the analytic instrument following expiration of the third holding period of time.

### Claim 19 (depends on 11)

The method of claim 11, wherein the analytic instrument includes a mass spectrometer.

### Claim 20 (depends on 19)

The method of claim 19, wherein the mass spectrometer includes an electrospray ionization mass spectrometer.
