A device for separating analytes is disclosed. The device has a sample injector, sample injection needle, sample reservoir container in communication with the sample injector, chromatography column downstream of the sample injector, and fluid conduits connecting the sample injector and the column. The interior surfaces of the fluid conduits, sample injector, sample reservoir container, and column form a flow path having wetted surfaces. A portion of the wetted surfaces of the flow path are coated with an alkylsilyl coating that is inert to at least one of the analytes. The alkylsilyl coating has the Formula I: ##STR00001##
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are each independently selected from (C.sub.1-C.sub.6)alkoxy, —NH(C.sub.1-C.sub.6)alkyl, —N((C.sub.1-C.sub.6)alkyl).sub.2, OH, OR.sup.A, and halo. R.sup.A represents a point of attachment to the interior surfaces of the fluidic system. At least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is OR.sup.A. X is (C.sub.1-C.sub.20)alkyl, —O[(CH.sub.2).sub.2O].sub.1-20—, —(C.sub.1-C.sub.10)[NH(CO)NH(C.sub.1-C.sub.10)].sub.1-20—, or —(C.sub.1-C.sub.10)[alkylphenyl(C.sub.1-C.sub.10)alkyl].sub.1-20-.

A device for separating analytes is disclosed. The device has a sample injector, sample injection needle, sample reservoir container in communication with the sample injector, chromatography column downstream of the sample injector, and fluid conduits connecting the sample injector and the column. The interior surfaces of the fluid conduits, sample injector, sample reservoir container, and column form a flow path having wetted surfaces. A portion of the wetted surfaces of the flow path are coated with an alkylsilyl coating that is inert to at least one of the analytes. The alkylsilyl coating has the Formula I: ##STR00001##
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are each independently selected from (C.sub.1-C.sub.6)alkoxy, —NH(C.sub.1-C.sub.6)alkyl, —N((C.sub.1-C.sub.6)alkyl).sub.2, OH, OR.sup.A, and halo. R.sup.A represents a point of attachment to the interior surfaces of the fluidic system. At least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is OR.sup.A. X is (C.sub.1-C.sub.20)alkyl, —O[(CH.sub.2).sub.2O].sub.1-20—, —(C.sub.1-C.sub.10)[NH(CO)NH(C.sub.1-C.sub.10)].sub.1-20—, or —(C.sub.1-C.sub.10)[alkylphenyl(C.sub.1-C.sub.10)alkyl].sub.1-20-.

A device for processing samples is disclosed. Interior surfaces of the device, which come in contact with fluids, define wetted surfaces. A portion of the wetted surfaces are coated with an alkylsilyl coating having the Formula I: ##STR00001##
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are each independently selected from (C.sub.1-C.sub.6)alkoxy, —NH(C.sub.1-C.sub.6)alkyl, —N((C.sub.1-C.sub.6)alkyl).sub.2, OH, OR.sup.A, and halo. R.sup.A represents a point of attachment to the interior surfaces of the fluidic system. At least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is OR.sup.A. X is (C.sub.1-C.sub.20)alkyl, —O[(CH.sub.2).sub.2O].sub.1-20—, —(C.sub.1-C.sub.10)[NH(CO)NH(C.sub.1-C.sub.10)].sub.1-20—, or —(C.sub.1-C.sub.10)[alkylphenyl(C.sub.1-C.sub.10)alkyl].sub.1-20—.

A device for processing samples is disclosed. Interior surfaces of the device, which come in contact with fluids, define wetted surfaces. A portion of the wetted surfaces are coated with an alkylsilyl coating having the Formula I: ##STR00001##
R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are each independently selected from (C.sub.1-C.sub.6)alkoxy, —NH(C.sub.1-C.sub.6)alkyl, —N((C.sub.1-C.sub.6)alkyl).sub.2, OH, OR.sup.A, and halo. R.sup.A represents a point of attachment to the interior surfaces of the fluidic system. At least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is OR.sup.A. X is (C.sub.1-C.sub.20)alkyl, —O[(CH.sub.2).sub.2O].sub.1-20—, —(C.sub.1-C.sub.10)[NH(CO)NH(C.sub.1-C.sub.10)].sub.1-20—, or —(C.sub.1-C.sub.10)[alkylphenyl(C.sub.1-C.sub.10)alkyl].sub.1-20—.

The present disclosure discusses a method of separating a sample (e.g., pharmaceutical drug, genotoxic impurity, biomarker, and/or biological metabolite) including coating a metallic flow path of a chromatographic system; injecting the sample into the chromatographic system; flowing the sample through the chromatographic system; separating the sample; and analyzing the separated sample using mass spectroscopy. In some examples, the coating applied to the surfaces defining the flow path is non-binding with respect to the sample—and the separated sample. Consequently, the sample does not bind to the low-binding surface of the coating of the flow path. The applied coating can increase the chromatographic peak area for the sample of the chromatographic system.

The disclosure provides systems and methods useful for predicting or detecting a malfunction in a chromatography process in real-time. In some embodiments, the disclosure provides systems and methods for detecting an atypical profile in a process chromatogram in ion-exchange chromatography of a biologic product.

The disclosure provides systems and methods useful for predicting or detecting a malfunction in a chromatography process in real-time. In some embodiments, the disclosure provides systems and methods for detecting an atypical profile in a process chromatogram in ion-exchange chromatography of a biologic product.

Chromatography apparatus and methods are described, especially for expanded bed adsorption. A column tube has a process fluid input device at the bottom and a movable piston in the top. The piston is enclosed in the column by a cover plate. The piston body has an inflatable seal, and is connected by a frame to a contact ring which carries another inflatable member to contact the tube wall. Process fluid leaves the operating volume through an opening of the piston and flexible hose, through the enclosed space and out through the cover plate. The space above the piston can be pressurised to control piston movement. The contact ring maintains piston alignment. The inflatable seals are used to fix the piston in position, allow it to slide or allow washing. The piston outlet may include a vortex-inhibitor. Bed and piston levels may be monitored by ultrasound sensors.

The present disclosure discusses a method of separating a sample (e.g., pharmaceutical drug, genotoxic impurity, biomarker, and/or biological metabolite) including coating a metallic flow path of a chromatographic system; injecting the sample into the chromatographic system; flowing the sample through the chromatographic system; separating the sample; and analyzing the separated sample using mass spectroscopy. In some examples, the coating applied to the surfaces defining the flow path is non-binding with respect to the sample—and the separated sample. Consequently, the sample does not bind to the low-binding surface of the coating of the flow path. The applied coating can increase the chromatographic peak area for the sample of the chromatographic system.

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.