The technology generally relates to tailoring a back pressure regulator in a chromatographic system to reduce unswept volume within the back pressure regulator to achieve better sample detection and a reduction in chromatographic band distortion effects.

A methodology scales supercritical fluid chromatography (SFC) and/or carbon dioxide based chromatography methods between different system and/or column configurations. The methodology includes measuring an average mobile phase density during a first separation utilizing C02 as a mobile phase component and substantially duplicating the average density profile for a second separation. Substantial duplication of the average mobile phase density (e.g., within about 10%, 5%, 2.5%, 1%, 0.5%, 0.1 %, 0.05%) results in chromatography for both system and/or column configurations having similar selectivity and retention factors. Average mobile phase density may be, either measured directly, calculated, or approximated using average pressure or density measurements. The average pressure profile may be used as a close approximation to duplicate average density profiles between separations.

When a liquid in the column is replaced by carbon dioxide in a supercritical state in the chromatograph, an operation of a first pump is controlled by a flow rate control unit, and the carbon dioxide in the supercritical state is supplied at a constant pressure. Moreover, when a flow rate of the carbon dioxide in the supercritical state reaches a predetermined flow rate thereafter, the flow rate control unit controls an operation of the first pump so that the carbon dioxide in the supercritical state is supplied at a constant flow rate.

The present invention provides a dynamic interface system between an extraction device and a chromatographic purification device for separating and purifying substance(s) from a mixture or matrix. One embodiment is the Supercritical Fluid Interface (“SFI”) between Supercritical Fluid Extraction (“SFE”), and Supercritical Fluid Chromatography (“SFC”). The SFI is capable of interfacing; gas, subcritical and supercritical fluid extraction methods and pair with gas, subcritical and supercritical fluid chromatography technologies that operate within the pressure and temperature parameters of the SFI. The SFI can operate up to 200 degrees celsius and 5000 psi. This interface technology allows for an inline oil extraction and chromatographic separation, the SFI can pair extraction and chromatography with the same solvent in different mobile phases, whereas the extraction can be performed using CO.sub.2 as a solvent in sub-critical phase and the SFI can receive the subcritical solution and then increase pressure and/or temperature to achieve supercritical state as required for injection into supercritical fluid chromatography technologies. The SFI coupling between SFE and SFC can to extract and refine cannabinoids from the cannabis industrious, hemp, plant and can also be applied to improve efficiency in an industry that extracts and refines oils, through chromatography, from organic materials using a gas, or sub/supercritical fluid as a solvent and mobile phase.

There is provided a method of operating a liquid chromatography arrangement, the liquid chromatography arrangement comprising: a solvent pump arranged to flow a liquid solvent over a liquid chromatography column; a restrictor arranged to restrict the liquid solvent from leaving the liquid chromatography column; and a liquid pump arranged to provide liquid flow between the liquid chromatography column and the restrictor, the method comprising: flowing the liquid solvent through the liquid chromatography column using the solvent pump; and controlling a liquid pressure within the liquid chromatography column by providing a liquid flow between the liquid chromatography column and the restrictor using the liquid pump.

Certain embodiments of the invention provides a method for monitoring level of saturation of a chromatography media in a column, which method comprises measuring a first pressure at the inlet of an unloaded column; measuring a second pressure at the inlet from a loaded column; and comparing the first and second pressure measurement to determine the level of saturation of the chromatography media. Embodiments of the invention also provide related methods for controlling a chromatography system and methods for controlling a periodic counter current chromatography system, as well as a chromatography system suitable for use with the novel methods.

Exemplary embodiments are directed to devices, methods and systems capable of pressurization, generally involving a flow system that includes a pressurized reservoir, at least one pump including a pump control valve, an outlet port, a shut-off valve and a vent valve. The flow system is configured to be pressurized. The shut-off valve is disposed between the pressurized reservoir and the at least one pump. The vent valve is disposed between the at least one pump and the outlet port. The shut-off valve, the vent valve and the pump control valve of the at least one pump are configured to actuate in a coordinated manner to control a pressurization of the flow system. Exemplary embodiments are further directed to devices, methods and systems for column switching, generally including at least a first column, a second column and a column switching valve.

A liquid chromatography monitoring system comprises a computer or electronic controller comprising computer-readable instructions operable to: (a) draw a fluid into a syringe pump; (b) configure a valve so as to fluidically couple the pump to either a fluidic pathway through a fluidic system or to a plug that prevents fluid flow; (c) cause the syringe pump to progressively compress the fluid therein or expel the fluid to the fluidic pathway, while measuring a pressure of the fluid; (d) determine a profile of the variation of the measured pressure; (e) compare the determined profile to an expected profile that depends upon the fluid; and (f) provide a notification of a sub-optimal operating condition or malfunction if the determined profile varies from the expected profile by greater than a predetermined tolerance.

Provided are methods for determining the apolipoprotein E (ApoE) phenotype in a sample by mass spectrometry; wherein the ApoE allele(s) present in the sample is determined from the identity of the ions detected by mass spectrometry. In another aspect, provided herein are methods for diagnosis or prognosis of Alzheimer's disease or dementia.

A sample injector configured to introduce a sample fluid into a mobile phase, wherein the mobile phase is to be driven by a mobile phase drive through a separation unit for separating compounds of the sample fluid in the mobile phase, wherein the sample injector comprises a metering device being operable for displacing fluid and for intaking a metered amount of the sample fluid into the sample injector, an injector valve being switchable for operating the sample injector selectively in a sample intake mode in which the metering device is operable to intake the sample fluid from a sample container, or a separation mode in which intaken sample fluid is driven between the mobile phase drive and the separation unit for separating the compounds, and a flow direction controller configured for defining an enabled flow direction of fluid displaced by the metering device and for defining a disabled flow direction.