Abstract: Provided are systems and methods for adapting to volume variations in microfluidic chromatography columns. A column is calibrated by comparing a parameter of the column with a same parameter of a reference column and generating, by a processor, an adjustment factor in response to the comparison between the parameter of the column with a same parameter of the reference column. Volume differences between the calibrated column and the reference column are compensated for by integrating the generated adjustment factor into a sample separation involving the calibrated column.

Abstract: Flow through pressure sensors for use in fluid chromatography systems include a planar device formed from diffusion bonding of a plurality of metallic sheets and at least one sensing element. The planar device has a top surface, a bottom surface and a flow through channel. A diaphragm formed from a portion of one of the top or bottom surfaces is located adjacent to a sensing region of the flow through channel and is attached to the sensing element. The diaphragm is sized to deflect a distance in response to fluid pressure in the sensing region, which has an internal volume of less than about 25 microliters. The diaphragm and attached sensing element form a pressure sensor that measures strain or deflection of the diaphragm to calculate a pressure within the sensing region.

Abstract: Variable-volume injection valves include a stator and a rotor. The stator has a first port, a second port, and a contact surface with a groove therein. The first port opens into the stator groove. The rotor has a contact surface with a groove therein. The contact surface of the rotor is urged against the contact surface of the stator such that the rotor groove opposes the stator groove with one end of the rotor groove overlapping the stator groove and the opposite end of the rotor groove overlapping the second port of the stator. The overlapping grooves of the rotor and stator provide a fluidic channel between the first and second ports of the stator. The rotor is movable with respect to the stator in order to vary a length of overlap between their overlapping grooves.

Abstract: The invention provides interfaces between analytical instruments, e.g., between chromatography systems and mass spectrometers. In an exemplary embodiment, an ion source is provided for connecting a carbon dioxide-based chromatograph device to a mass spectrometer. The ion source includes a first conduit for receiving eluent from the chromatography device, a heater for heating at least a portion of said first conduit, a second conduit in fluid communication with the first conduit, an inlet for receiving eluent from said second conduit and introducing the eluent into an ion source region to form a plume of gas and/or liquid in the ion source region, and an ionization promoting inlet for injecting an ionization promoting fluid into the ion source region to interact with the plume to promote ionization of at least some of the plume.

Abstract: One aspect of the invention provides a flow sensing apparatus including: a fluid channel that allows a fluid to flow in a first direction; a first thermoelectric sensing element arranged at a first position along the fluid channel such that it senses a temperature of the fluid; a second thermoelectric sensing element arranged at a second position along the fluid channel and separated from the first sensing element by a predetermined distance along the fluid channel; and a heating element arranged between the first and second thermoelectric sensing elements, the heating element being equally spaced from the first and second thermoelectric sensing elements.

Abstract: A system (e.g., a chromatography system) includes a rotor, a microfluidic device, a rotor driver, a clamping mechanism, and control electronics. The rotor defines a plurality of first fluid-conveying features. The micro fluidic device defines one or more channels and a plurality of second fluid-conveying features, in fluid communication with the one or more channels. The rotor driver is coupled to the rotor and is configured to rotate the rotor, relative to the microfluidic device, between a first position and a second position such that, in each of the positions, at least one of the first fluid-conveying features cooperates with at least one of the one or more channels to provide for fluid communication therebetween. The clamping mechanism is operable to provide a sealing force to establish a fluid-tight seal between the rotor and the microfluidic device.

Abstract: An apparatus for use in a chromatography system includes a microfluidic substrate having a fluidic channel configured as an analytical chromatographic column and a fluidic port on one side of the microfluidic substrate. The fluidic port opens at a head end of the analytical chromatographic column. A dried blood spot (DBS) collection device holds one or more dried biological samples. The DBS collection device is directly coupled to the microfluidic substrate whereby one of the biological samples is placed into fluidic communication with the fluidic channel of the microfluidic substrate and an extraction of that biological sample flows toward the head end of the analytical chromatographic column. A diluent source fluidically coupled to the fluidic port supplies a solvent to the head end of the analytical column to dilute the extracted biological sample before the biological sample flows into the analytical chromatographic column.

Abstract: An electrokinetic pump can be used to deliver calibrant (“lock mass”) ions to a mass spectrometer for calibration of a mass spectrometry system. Electrokinetically controlled calibrant delivery can help to eliminate the need for the more cumbersome mechanisms that are often used for ion delivery. In addition, electrokinetically controlled calibrant delivery can provide for a more user-friendly system in which a calibrant solution can be packaged into a disposable cartridge. Furthermore, when implemented in a microfluidic format, electrokinetically controlled calibrant delivery can be coupled with an electrokinetically controlled separation system, such as capillary electrophoresis (CE), to allow efficient solid-state switching between analytical and calibrant sprays.

Abstract: A method and apparatus for monitoring and controlling nano-scale flow rate of fluid in the operating flow path of a HPLC system provide fluid flow without relying on complex calibration routines to compensate for solvent composition gradients typically used in HPLC. The apparatus and method are used to correct the flow output of a typical, analytical-scale (0.1-5 mL/min) HPLC pump to enable accurate and precise flow delivery at capillary (<0.1 mL/min) and nano-scale (<1 ?L/min) HPLC flow rates.

Abstract: A method and apparatus for monitoring and controlling nano-scale flow rate of fluid in the operating flow path of a HPLC system provide fluid flow without relying on complex calibration routines to compensate for solvent composition gradients typically used in HPLC. The apparatus and method are used to correct the flow output of a typical, analytical-scale (0.1-5 mL/min) HPLC pump to enable accurate and precise flow delivery at capillary (<0.1 mL/min) and nano-scale (<1 ?L/min) HPLC flow rates.

Abstract: A method and apparatus for monitoring and controlling the nano-scale flow rate of fluid in the operating flow path of a HPLC system without relying on a nano-scale sensor in the operating flow path. A main flow sensor is disposed in the main flow path between the pump and a flow-divider. A waste flow sensor is disposed in the waste flow path downstream of the splitter. The output signal of the waste flow sensor is subtracted from the output signal of the main flow sensor in a difference circuit. The difference signal is divided by the output signal from the main flow sensor in a divider circuit. The output of the divider circuit represents an empirical split ratio of the flow-divider and is independent of media composition.

Abstract: A check valve includes a valve seat and a compliant member that moves to seal the check valve by contacting the valve seat. A method for priming a chromatography solvent pump includes providing the check valve in fluid communication with an outlet of the pump, drawing fluid into the pump from a fluid source, and expelling the fluid from the pump through the valve, thus wetting the check valve. Another method for priming a chromatography solvent pump includes providing the check valve in fluid communication with an inlet of the pump, drawing fluid through the valve into the pump, and expelling the fluid from the pump.

Abstract: A fluid controller apparatus controls fluid flow, such as a solvent gradient flow, in a chromatography system. An apparatus includes a fluid-gradient controller having a fluid reservoir for containing a pump fluid and a pumping device connected to the fluid reservoir for receiving the pump fluid. The pumping device is in fluid communication with parallel-configured first and second solvent lines. The first and second solvent lines each contain a restrictor element and a solvent reservoir. During operation, the pumping device causes the pump fluid to flow through the first and second solvent lines in relation to their respective restriction devices. The pump fluid displaces solvent within the solvent reservoirs. The displaced solvent is mixed to form a solvent gradient.

Abstract: Variable-volume injection valves include a stator and a rotor. The stator has a first port, a second port, and a contact surface with a groove therein. The first port opens into the stator groove. The rotor has a contact surface with a groove therein. The contact surface of the rotor is urged against the contact surface of the stator such that the rotor groove opposes the stator groove with one end of the rotor groove overlapping the stator groove and the opposite end of the rotor groove overlapping the second port of the stator. The overlapping grooves of the rotor and stator provide a fluidic channel between the first and second ports of the stator. The rotor is movable with respect to the stator in order to vary a length of overlap between their overlapping grooves.

Abstract: Flow through pressure sensors for use in fluid chromatography systems include a planar device formed from diffusion bonding of a plurality of metallic sheets and at least one sensing element. The planar device has a top surface, a bottom surface and a flow through channel. A diaphragm formed from a portion of one of the top or bottom surfaces is located adjacent to a sensing region of the flow through channel and is attached to the sensing element. The diaphragm is sized to deflect a distance in response to fluid pressure in the sensing region, which has an internal volume of less than about 25 microliters. The diaphragm and attached sensing element form a pressure sensor that measures strain or deflection of the diaphragm to calculate a pressure within the sensing region.

Abstract: Described is a device for collecting a fluid sample, such as a biological fluid sample. The device includes a planar collection substrate having an absorbent material. The planar collection substrate includes an impermeable region and a sample collection region. The impermeable region is impermeable to the fluid sample and is embedded in the planar collection substrate in a spatial pattern. The sample collection region is in an area excluded from the spatial pattern and has a shape and a size defined by the spatial pattern. The sample collection region is configured to receive a known volume of the fluid sample. In an alternative form, the device includes a sample collection element disposed in an impermeable planar holder and, in another alternative form, the device includes an absorbent material disposed inside an impermeable tube wall.

Abstract: One aspect of the invention provides a flow sensing apparatus for sensing fluid flow in a nano-scale high-performance liquid chromatography apparatus. The flow sensing apparatus includes: a fluid channel that allows a fluid to flow in a first direction; a first infrared sensor arranged at a first position along the fluid channel such that it senses a temperature of the fluid; a second infrared sensor arranged at a second position along the fluid channel and separated from the first sensor by a predetermined distance along the fluid channel; and a heating element arranged between the first and second infrared sensors. The heating element is equally spaced from the first and second infrared sensors.

Abstract: One aspect of the invention provides a flow sensing apparatus including: a fluid channel that allows a fluid to flow in a first direction; a first temperature sensor arranged at a first position along the fluid channel; a second temperature sensor arranged at a second position along the fluid channel and separated from the first sensor by a predetermined distance along the fluid channel; a heating element arranged between the first and second thermoelectric sensors, the heating element being substantially equally spaced from the first and second thermoelectric sensors; a heating element temperature sensor for sensing a temperature of the heating element; and a control device configured to maintain the heating element at a substantially uniform temperature.

Abstract: One aspect of the invention provides a flow sensing apparatus including: a fluid channel that allows a fluid to flow in a first direction; a first thermoelectric sensing element arranged at a first position along the fluid channel such that it senses a temperature of the fluid; a second thermoelectric sensing element arranged at a second position along the fluid channel and separated from the first sensing element by a predetermined distance along the fluid channel; and a heating element arranged between the first and second thermoelectric sensing elements, the heating element being equally spaced from the first and second thermoelectric sensing elements.

Abstract: A chromatography apparatus includes a sample-delivery patterned substrate and a tube-based separation column directly connected to an outlet port of the patterned substrate. The patterned substrate includes an injector valve connected to the outlet port.