# US 10,371,673 B2 · Carbon dioxide based chromatography systems including multiple carbon dioxide pumps > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,371,673 B2 - Document ID: US10371673B2 - Status: Granted - Kind: B2 - Application number: 15/909,264 - Filed: 2018-03-01 - Published: 2018-09-06 - Granted: 2019-08-06 - Earliest claimed: 2017-03-03 - Assignees: Waters Technologies Corporation - Applicants: Waters Technologies Corporation - Inventors: Michael O. Fogwill; Joseph A. Jarrell; Joseph D. Michienzi; Thomas S. McDonald - Web page: https://patentgrep.com/patent/US10371673B2 ## CPC - G01N 30/32: of pressure or speed (G01N30/36 takes precedence) - B01D 15/163: {Pressure or speed conditioning} - B01D 15/40: using supercritical fluid as mobile phase or eluent - G01N 30/34: of fluid composition, e.g. gradient (G01N30/36 takes precedence) - G01N 30/36: in high pressure liquid systems - G01N 30/62: Detectors specially adapted therefor - G01N 30/7233: {interfaced to liquid or supercritical fluid chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04)} - G01N 2030/326: {pumps} - G01N 2030/347: {mixers} - G01N 2030/623: {by modulation of sample feed or detector response} - 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) - 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) ## Abstract The present disclosure relates to methodologies, systems and apparatus for controlling pressure in a CO2-based chromatography system. A first CO2 pump operates in constant flow mode and delivers CO2 to a chromatography column, and liquid modifier is introduced to the chromatography column according to a gradient. A second CO2 pump is disposed downstream of the column and operates in constant pressure mode to introduce CO2 into a flow stream at an output of the column. Liquid modifier is also introduced into the flow stream at the output of the column according to a reverse gradient compared to the gradient entering the chromatography column. ## Claims ### Claim 1 A method of maintaining pressure in a CO2-based chromatography system, the method comprising: introducing CO2 into a mixer via a first CO2 pump; introducing liquid modifier into a mixer via a first liquid modifier pump; receiving a mixture of CO2 and liquid modifier from the mixer at a chromatography column; introducing CO2 into a flow stream at an output of the column via a second CO2 pump; introducing liquid modifier into the flow stream at the output of the column via a second liquid modifier into pump; controlling the second CO2 pump to deliver liquid modifier according to a reverse pressure downstream of the column; and controlling the second liquid modified pump to deliver liquid modifier according to a reverse gradient compared to a gradient introduced into the column from the first liquid modifier pump. ### Claim 2 (depends on 1) The method of claim 1, further comprising introducing the flow stream at the output of the column into a detector. ### Claim 3 (depends on 2) The method of claim 2, further comprising controlling the second liquid modifier pump such that a total flow rate of liquid modifier entering the detector is constant. ### Claim 4 (depends on 2) The method of claim 2, wherein the detector is a flame ionization detector or a mass spectrometer. ### Claim 5 (depends on 1) The method of claim 1, wherein the first CO2 pump operates in a constant flow mode, and the second CO2 pump operates in a constant pressure mode. ### Claim 6 (depends on 1) The method of claim 1, wherein the second CO2 pump and the second liquid modified pump introduce fluid into the flow stream at the output of the column via a tee fitting. ### Claim 7 (depends on 1) The method of claim 1, wherein the second CO2 pump and the second liquid modifier pump introduce fluid into the flow stream at the output of the column via a tee fitting. ### Claim 8 (depends on 7) The method of claim 7, further comprising directing an output of the tee fitting to a detector via a fixed restrictor. ### Claim 9 A CO2-based chromatography system comprising: a first CO2 pump disposed to deliver CO2 to a chromatography column; a liquid modifier pump; a second CO2 pump located downstream of the column and disposed to operate independently of the first CO2 pump to introduce CO2 into a flow stream at an output of the column, the second CO2 pump operating in constant pressure mode in order to maintain a target pressure; and an active splitter disposed to receive a liquid modifier from the liquid modifier pump, the active splitter disposed to deliver liquid modifier to the chromatography column according to a gradient, and further disposed to introduce liquid modifier into the flow stream at the output of the column according to a reverse gradient compared to the gradient entering the chromatography column. ### Claim 10 A CO2 based-pump system comprising: a CO2 pump; a liquid modifier pump; a first active splitter disposed to receive a liquid modifier from the liquid modifier pump, introduce the liquid modifier to a chromatography column according to a gradient, and introduce the liquid modifier into a flow stream downstream of the chromatography column according to a reverse gradient compared to the gradient entering the chromatography column; and a second active splitter disposed to receive CO2 from the CO2 pump, introduce CO2 to the chromatography column, and introduce CO2 into the flow stream downstream of the chromatography column to maintain a target pressure.