Apparatuses and associated methods are described for the efficient evaluation of C1-containing substrates, and especially for such evaluation conducted locally, or on-site, at a prospective facility for implementation of a biological conversion process for desired end product using a C1 carbon source. The exact composition of a given, industrial C1-containing substrate, as well as the range in composition fluctuations, are generally difficult to reproduce at a remote facility (e.g., a laboratory or a pilot-scale or demonstration-scale process), as required for the accurate prediction/modeling of commercial performance to justify large capital expenditures for commercial scale-up.

Separation of materials is achieved using affinity binding and acoustophoretic techniques. A column provided with a fluid mixture of materials for separation and support structures may be used with acoustic waves to block flow of the support structures. The support structures can have an affinity for one or more materials in the fluid mixture. By blocking flow of the support structures, materials bound or adhered to the support structure are also blocked.

Apparatuses and associated methods are described for the efficient evaluation of C1-containing substrates, and especially for such evaluation conducted locally, or on-site, at a prospective facility for implementation of a biological conversion process for desired end product using a C1 carbon source. The exact composition of a given, industrial C1-containing substrate, as well as the range in composition fluctuations, are generally difficult to reproduce at a remote facility (e.g., a laboratory or a pilot-scale or demonstration-scale process), as required for the accurate prediction/modeling of commercial performance to justify large capital expenditures for commercial scale-up.

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).

Separation of materials is achieved using affinity binding and acoustophoretic techniques. A column provided with a fluid mixture of materials for separation and support structures may be used with acoustic waves to block flow of the support structures. The support structures can have an affinity for one or more materials in the fluid mixture. By blocking flow of the support structures, materials bound or adhered to the support structure are also blocked.

A method of performing a chromatographic separation includes modulating a portion of a flowstream to a trap column to retain at least one analyte from the flowstream on the trap column. A flow of a modifier is provided through the trap column to generate an elution comprising the at least one analyte. A flow of a compressible fluid-based chromatography (CFC) mobile phase or CFC solvent is merged with the elution from the trap column to generate a diluted elution. Carbon dioxide may be used as the CFC solvent or as a component of the CFC mobile phase. The diluted elution is provided to a CFC column where at least one analyte is focused at a head of the CFC column. Examples of a flowstream that may be used include an eluent from a chromatography column or a fluid flow from an extraction system.

A method of performing a chromatographic separation includes modulating a portion of a flowstream to a trap column to retain at least one analyte from the flowstream on the trap column. A flow of a modifier is provided through the trap column to generate an elution comprising the at least one analyte. A flow of a compressible fluid-based chromatography (CFC) mobile phase or CFC solvent is merged with the elution from the trap column to generate a diluted elution. Carbon dioxide may be used as the CFC solvent or as a component of the CFC mobile phase. The diluted elution is provided to a CFC column where at least one analyte is focused at a head of the CFC column. Examples of a flowstream that may be used include an eluent from a chromatography column or a fluid flow from an extraction system.

Apparatus for processing a liquid comprising a target substance, preferably a biomolecule, is provided. The apparatus comprises at least a first and a second means for carrying out a unit operation, each means for carrying out a unit operation comprising a feed for a liquid in fluid connection with the inlet of a flow-controller comprising a variable flow inlet valve and an outlet, wherein at least one of the means for carrying out a unit operation comprises feeds for at least two liquids, the feeds being in fluid connection with the inlets of a multiple inlet flow-controller comprising two or more variable flow inlet valves for dosing the at least two liquids, the flow-controller also comprising an outlet; a feed for a liquid feedstock comprising the target substance in fluid connection with the outlet from the flow-controller thereby to enable combination of the feed for a liquid comprising the target substance with the mixed bioprocessing liquids to produce a device feed; a device for achieving a processing operation comprising a device inlet and a device outlet, the device inlet being in fluid connection with the device feed; and a means for imparting flow through the flow controller and from the feed for the liquid feedstock through the processing device via the device inlet; and wherein the feed for a liquid feedstock comprising the target substance for the second means for carrying out a unit operation comprises the outlet from the first means for carrying out a unit operation.

One aspect of the invention provides a liquid chromatography system including: a first solvent manager configured to dispense various ratios of a first solvent and a second solvent; a first column in fluid communication with the first solvent manager; a mixer in fluid communication with the first column; a first valve in fluid communication with the mixer; a second column having a first end in fluid communication with a first port of the first valve and a second end in fluid communication with a second port of the first valve; a second solvent manager adapted and configured to dispense various ratios of a third solvent and a fourth solvent; and a second valve in fluid communication with the second solvent manager, the first valve, and the mixer. The first valve and the second valve are adapted and configured for actuation between and a second position. In the first position: solvent dispensed by the first solvent manager and an injected sample flow over the first column; eluent from the first column is mixed with solvent dispensed by the second solvent manager in the mixer to produce a combined mobile phase; and the combined mobile phase is passed through the first valve and over the second column in a first direction to trap analytes of interest on the first column. In the second position, solvent dispensed by the second solvent manager is passed over the second column in a second direction to release the analytes of interest from the second column.

A multidimensional liquid chromatography separation system has a mobile-phase storage tank, a first liquid transfer device, a second liquid transfer device, a first sample introduction device, a second sample introduction device, a separation device, a collection, storage device, at least two drainage devices and a flow path switching device. A separation method for protein separation using the multidimensional liquid chromatography separation system has the steps of: 1) preparation in advance, 2) the first dimensional separation, 3) collection and storage of the intermediate fraction, 4) the second dimensional or multidimensional separation and repeating the steps 3) and 4).