Provided are two-dimensional chromatography systems and methods for separating and/or analyzing complex mixtures of organic compounds. In particularly, a two-dimensional reversed-phase liquid chromatography (RPLC)supercritical fluid chromatography (SFC) system is described including a trapping column at the interface which collects the analytes eluted from the first dimension chromatography while letting the RPLC mobile phase pass through. The peaks of interest from the RPLC dimension column are effectively focused as sharp concentration pulses on the trapping column, which is subsequently injected onto the second dimension SFC column. The system can be used for simultaneous achiral and chiral analysis of pharmaceutical compounds. The first dimension RPLC separation provides the achiral purity result, and the second dimension SFC separation provides the chiral purity result (enantiomeric excess).

In a method for processing successive fluidic sample portions provided by a sample source, sample reception volumes are filled successively temporarily with at least a respective one of the sample sections, and the sample sections are emptied successively out of the sample reception volumes in such a way, that, while emptying, it is avoided to bring two respective ones of the sample sections, which have not left the sample source directly adjacent to one another, in contact with one another.

A chromatography system includes a first chromatography column for receiving and separating a flow stream, a plurality of traps configured to trap a plurality of distinct flow segments exiting the first chromatography column during separation of the flow stream, and a second chromatography column operatively associated with the plurality of traps for receiving and separating the distinct flow segments. The system can include at-column dilution at trapping and separating stages thereof. A chromatography method for operating the chromatographic system includes measuring a plurality of time segments corresponding to a plurality of peaks of a fluid sample flowing through the first chromatographic column, and sequentially fluidly coupling the plurality of distinct flow segments with the corresponding plurality of traps during time segments corresponding to the plurality of peaks.

Provided are two-dimensional chromatography systems and methods for separating and/or analyzing complex mixtures of organic compounds. In particularly, a two-dimensional reversed-phase liquid chromatography (RPLC)supercritical fluid chromatography (SFC) system is described including a trapping column at the interface which collects the analytes eluted from the first dimension chromatography while letting the RPLC mobile phase pass through. The peaks of interest from the RPLC dimension column are effectively focused as sharp concentration pulses on the trapping column, which is subsequently injected onto the second dimension SFC column. The system can be used for simultaneous achiral and chiral analysis of pharmaceutical compounds. The first dimension RPLC separation provides the achiral purity result, and the second dimension SFC separation provides the chiral purity result (enantiomeric excess).

The present disclosure relates to the determination of analytes in a sample using chromatography. The present disclosure provides methods of separating an analyte from a sample. The method includes introducing a sample comprising the analytes into a chromatographic system. The chromatographic system has a flow path disposed in an interior of the chromatographic system, at least a portion of the flow path having an active coating, and a chromatographic column having a stationary phase material in an interior of the chromatographic column that facilitates separation of the analytes in the sample through interaction with at least one analyte in the sample. The active coating is selected to interact with at least one analyte in the sample through (1) a repulsive force, (2) a secondary interaction, or (3) a retention mechanism distinct from the interaction with the stationary phase material.

A multi-dimensional liquid analysis system includes a first dimension system and a second dimension system, wherein outflow from the first dimension system is separated at a flow splitter under controlled conditions. The flow splitter separates the first dimension outflow into first and second split outlet flows, with one of the split outlet flows being metered to a designated flow rate with a flow metering device disposed downstream from the flow splitter. The flow metering device selectively closes or opens an outlet flow path to define a volumetric flow rate along that outlet flow path, so that the other split outlet flow is correspondingly controlled.

The present disclosure relates to an enhanced multi-dimensional chromatography system and method using selectable At-Column Dilution to improve compatibility of the interface and transfer between the multiple dimensions. The use of At-Column Dilution (ACD) with multi-dimensional chromatography can provide greater retention of the diverted components on subsequent stationary phases, and increase the sensitivity and peak shape of the component(s) separated on subsequent dimensions.

Described are an interface module for two-dimensional chromatography and a method of performing a chromatographic separation that may use the interface module. The interface module includes a valve module, a collection needle, a modifier module and a sample storage element. The valve module has a first port configured to receive an eluent from a first chromatography system, a second port configured to provide a fraction obtained from the eluent, a third port and a fourth port. The collection needle and the modifier module are in fluidic communication with the valve module at the third and fourth ports, respectively. The modifier module includes a source of a modifier solvent. The sample storage element is in fluidic communication with the valve module and is configured to receive a volume of the fraction for injection as a sample into a second chromatography system.

Described are stator arrays for multi-valve systems used in different chromatographic applications. Also described is a mounting assembly for a multi-valve system that includes the stator array. Each stator array has a stator body having a first stator surface and a second stator surface. Each stator surface has a plurality of stator ports and is configured to engage a rotor surface of a rotary valve actuator. A fluid channel inside the stator body couples one of the stator ports of the first stator surface to one of the stator ports of the second stator surface. The fluid channel may be a microfluidic channel. A solid-state diffusion bonding process in which two or more parallel layers of material are joined together may be used to fabricate the stator body. Complex fluid channel networks may be formed using many fluid channels formed in multiple layers within the stator body.

An apparatus introduces a sample into a separation unit of a chromatography system with a mobile phase, including first and second mobile phase components. The apparatus includes first and second pump systems, and an injection unit. The first pump system provides the first mobile phase component, first and second portions of the first mobile phase component flowing through first and second branches, respectively. The second pump system provides the second mobile phase component, a first portion of the second mobile phase component flowing through a third branch. The injection unit receives a combined stream of the first portions of the first and second mobile phase components provided via the first and third branches, respectively, and injects the sample into the combined stream to form a sample-containing stream, which is subsequently combined with the second portion of the first mobile phase component to form a diluted sample-containing stream.