# US 10,307,691 B2 · Apparatus and methods for preparative liquid chromatography

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- Number: US 10,307,691 B2
- Document ID: US10307691B2
- Status: Granted
- Kind: B2
- Application number: 14/627,376
- Filed: 2015-02-20
- Published: 2015-06-18
- Granted: 2019-06-04
- Earliest claimed: 2008-09-12
- Assignees: Waters Technologies Corporation
- Applicants: Waters Technologies Corporation
- Inventors: Joshua A. Shreve; Michael R. Jackson
- Web page: https://patentgrep.com/patent/US10307691B2

## CPC

- B01D 15/18: relating to flow patterns
- B01D 15/00: Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D 15/08: Selective adsorption, e.g. chromatography
- B01D 15/10: characterised by constructional or operational features
- B01D 15/102: {Process control, e.g. determination or optimization of process parameters; Programmable logic control [PLC]}
- B01D 15/12: relating to the preparation of the feed
- B01D 15/14: relating to the introduction of the feed to the apparatus
- B01D 15/16: relating to the conditioning of the fluid carrier
- B01D 15/163: {Pressure or speed conditioning}
- B01D 15/166: {Fluid composition conditioning, e.g. gradient}
- B01D 15/267: {using neutral sorbents, e.g. activated carbon or diatomaceous earth}
- G01N 30/00: Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography {or field flow fractionation} (G01N3/00, G01N5/00, G01N7/00, G01N9/00, G01N11/00, G01N13/00, G01N15/00, G01N17/00, G01N19/00, G01N21/00, G01N22/00, G01N23/00, G01N24/00, G01N25/00, G01N27/00, G01N29/00 take precedence)
- G01N 30/02: Column chromatography
- G01N 30/04: Preparation or injection of sample to be analysed
- G01N 30/26: Conditioning of the fluid carrier; Flow patterns
- G01N 30/28: Control of physical parameters of the fluid carrier
- G01N 30/30: of temperature
- G01N 30/32: of pressure or speed (G01N30/36 takes precedence)
- G01N 30/34: of fluid composition, e.g. gradient (G01N30/36 takes precedence)
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- 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

A method of liquid chromatography includes providing one or more solvent reservoirs, providing a solvent pump, drawing one or more solvents into the pump in response to a pressure drop that promotes outgassing of the solvents, and dispersing outgassed bubbles into smaller bubbles to promote re-dissolution of the gas. A liquid-chromatography apparatus includes at least two solvent reservoirs, a pump, at least one bubble-dispersing unit that receives a pressurized flow of proportioned solvents from the pump, and a control unit. The control unit includes a processor and a memory that stores instructions; the control unit controls proportioning of solvents to obtain a preselected solvent composition, and pumping at flow rates to support preparative-scale or process-scale liquid chromatography.

## Claims

### Claim 1

A method of liquid chromatography, comprising:
providing at least one solvent reservoir containing at least one solvent having dissolved gas;
providing a pump comprising at least one piston disposed in a chamber in fluid communication with the at least one solvent reservoir;
drawing the at least one solvent into the pump in response to a pressure drop that promotes formation of bubbles due to outgassing of the at least one solvent; and
dispersing the bubbles into smaller bubbles, after the bubbles exit the pump and prior to an injector that is positioned between the pump and the column, to promote redissolution of the dissolved gas.

### Claim 2 (depends on 1)

The method of claim 1, whereby the drawing step comprises providing a pump flow rate.

### Claim 3 (depends on 1)

The method of claim 1, wherein the dispersing step comprises passing the bubbles through a component that fragments the bubbles.

### Claim 4 (depends on 1)

The method of claim 1, wherein the pressure drop is at least 14 pounds per square inch.

### Claim 5 (depends on 1)

The method of claim 1, further comprising providing a solvent mixer having an inlet in fluid communication with an outlet of the pump, wherein dispersing the bubbles comprises dispersing the bubbles after the bubbles exit the mixer.

### Claim 6 (depends on 5)

The method of claim 5, wherein providing the at least one solvent reservoir comprises providing a water reservoir and a methanol reservoir, thereby promoting the formation of bubbles in the mixer due to a decrease in gas solubility upon mixing of the water and methanol in the mixer.

### Claim 7 (depends on 2)

The method of claim 2, wherein the pump flow rate is at least 5 ml/minute.

### Claim 8 (depends on 2)

The method of claim 2, wherein the pump flow rate is at least 10 ml/minute.

### Claim 9 (depends on 2)

The method of claim 2, wherein the pump flow rate is at least 100 ml/minute.