Abstract: An apparatus for the high throughput measurement of optical properties of liquid samples placed into the wells of a multiwell plate is disclosed. An optical fiber within a fiber bundle containing no corrective optics between the fiber ends and the well plate bottom illuminates the sample in order to induce fluorescence, and multiple fibers collect emission radiation and transmit it to a fluorescence detector such as a spectrometer. Other embodiments involve a light scattering illumination source with detection fibers located in either the same bundle containing the fluorescence monitoring fibers or an independent light scattering detection bundle for the measurement of static and/or dynamic light scattering. Some embodiments of the invention permit the measurement of phase analysis light scattering. Thus the measurement of multiple optical properties of a liquid sample may be made simultaneously or in succession. A method for these measurements is also disclosed.

Abstract: A new liquid flow cell assembly for light scattering measurements is disclosed which utilized a floating manifold system. The assembly operates with minimal stacked tolerances by aligning the cell to the windows within a manifold and independently aligning the cell to the read head directly. This configuration enables the ability to replace the flow cell or the flow cell/manifold assembly within a light scattering instrument without the need to realign the flow through elements with the light scattering illumination source while still maintaining reproducible, quality data. Some embodiments employ wide bore cells which enable the measurement of process analytic technology (PAT) including online monitoring of reactions.

Abstract: The present invention an apparatus and method of injecting a liquid borne sample into a field flow fractionator and a method of forming a top plate and spacer. In an embodiment, the field flow fractionation unit includes a top plate including a sample injection inlet port, a sample injection outlet port, and a spacer including a separation channel cavity defining at least a portion of the separation channel, a sample injection inlet cavity configured to be in fluid contact with the separation channel and located substantially beneath the sample injection inlet port, a sample injection outlet cavity configured to be in fluid contact with the separation channel and located substantially beneath the sample injection outlet port, such that the injection inlet and outlet paths are configured to define an injection channel that is essentially perpendicular to the length of the separation channel spanning the width of the separation channel cavity.

Abstract: When measuring electrophoretic mobility it is customary to apply an electric field and determine the electrophoretic velocity while minimizing all other contributions to the particle movement. A method and apparatus for the measurement of mobility while the sample is flowing is disclosed. Combined with a fractionation system, this approach further enables the direct measurement of individual species' mobility within a multi-modal sample. Other advantages of this new mobility measurement approach include the ability to easily pressurize the sample to suppress electrolysis, mitigation of oxidation-reduction effects and efficient heat dissipation.

Abstract: An electrode for use in instruments capable of measuring the electrophoretic mobility of particles in solution is disclosed. The electrode is comprised of an inexpensive support member, generally made of titanium, onto a flat surface of which has been connected, generally by microwelding, a flat electrically conductive but chemically inert foil member, preferably platinum. A uniform texture can be generated on the exposed surfaces of the electrode by various means including tumbling the electrode with an abrasive. An oxide layer can be generated on the support member by soaking the composite electrode in an appropriate medium, protecting the exposed surface of the support member from fluid contact with the sample solution, while the foil member, unaffected by the oxidation process, is able to contact the sample solution.

Abstract: One or more homogenizing elements are employed in a flow through, multi-detector optical measurement system. The homogenizing elements correct for problems common to multi-detector flow-through systems such as peak tailing and non-uniform sample profile within the measurement cell. The homogenizing elements include coiled inlet tubing, a flow distributor near the inlet of the cell, and a flow distributor at the outlet of the cell. This homogenization of the sample mimics plug flow within the measurement cell and enables each detector to view the same sample composition in each individual corresponding viewed sample volume. This system is particularly beneficial when performing multiangle light scattering (MALS) measurements of narrow chromatographic peaks such as those produced by ultra-high pressure liquid chromatography (UHPLC).

Abstract: A method and apparatus are disclosed which enable the reduction of sample carryover in the measurement cell of an analytical instrument. A sample cell is defined as a region sealed within a first o-ring. Located outside of said sample region is another o-ring which seals and defines a seal wash region as the region between the first and second o-ring. After the fluid sample is injected into the measurement cell a pressure is applied to the seal wash region, forcing the first o-ring to the innermost extent of the groove in which it sits, expelling any trapped solvent and removing from the measurement cell a significant dead volume while the cell is flushed and prepared for a new sample and corresponding measurement.

Abstract: An apparatus for the high throughput measurement of optical properties of liquid samples placed into the wells of a multiwell plate is disclosed. An optical fiber within a fiber bundle containing no corrective optics between the fiber ends and the well plate bottom illuminates the sample in order to induce fluorescence, and multiple fibers collect emission radiation and transmit it to a fluorescence detector such as a spectrometer. Other embodiments involve a light scattering illumination source with detection fibers located in either the same bundle containing the fluorescence monitoring fibers or an independent light scattering detection bundle for the measurement of static and/or dynamic light scattering. Some embodiments of the invention permit the measurement of phase analysis light scattering. Thus the measurement of multiple optical properties of a liquid sample may be made simultaneously or in succession. A method for these measurements is also disclosed.

Abstract: A new liquid flow cell assembly for light scattering measurements is disclosed which utilized a floating manifold system. The assembly operates with minimal stacked tolerances by aligning the cell to the windows within a manifold and independently aligning the cell to the read head directly. This configuration enables the ability to replace the flow cell or the flow cell/manifold assembly within a light scattering instrument without the need to realign the flow through elements with the light scattering illumination source while still maintaining reproducible, quality data. Some embodiments employ wide bore cells which enable the measurement of process analytic technology (PAT) including online monitoring of reactions.

Abstract: A method and apparatus for measuring the physical properties of a drug formulation suspended in a pressurized liquid propellant and a system to enable such measurements is disclosed. Drug formulations suspended in pressurized liquid propellant used in Pressurized Metered Dose Inhalers (pMDIs) are propelled in their native liquid state into an analytical instrument with a measurement cell capable of withstanding the pressure required to retain the sample in liquid form by employing a device to rapidly release the contents of the pMDI canister into the measurement instrument wherein the sample's electrophoretic mobility and size may be determined by MP-PALS or other techniques. A series of valves permits the maintenance of the high pressure in the system. Once the measurements are made, the pressurized liquid is allowed to pass to waste or another analytical instrument by opening an exit valve.

Abstract: When measuring electrophoretic mobility it is customary to apply an electric field and determine the electrophoretic velocity while minimizing all other contributions to the particle movement. A method and apparatus for the measurement of mobility while the sample is flowing is disclosed. Combined with a fractionation system, this approach further enables the direct measurement of individual species' mobility within a multi-modal sample. Other advantages of this new mobility measurement approach include the ability to easily pressurize the sample to suppress electrolysis, mitigation of oxidation-reduction effects and efficient heat dissipation.

Abstract: One or more homogenizing elements are employed in a flow through, multi-detector optical measurement system. The homogenizing elements correct for problems common to multi-detector flow-through systems such as peak tailing and non-uniform sample profile within the measurement cell. The homogenizing elements include coiled inlet tubing, a flow distributor near the inlet of the cell, and a flow distributor at the outlet of the cell. This homogenization of the sample mimics plug flow within the measurement cell and enables each detector to view the same sample composition in each individual corresponding viewed sample volume. This system is particularly beneficial when performing multiangle light scattering (MALS) measurements of narrow chromatographic peaks such as those produced by ultra-high pressure liquid chromatography (UHPLC).

Abstract: A method and apparatus are disclosed for the collection of light scattered from a liquid sample contained within a multiwell plate for which evaporation from the wells is mitigated by the application of a barrier between the liquid sample and the environment. A vertical thermal gradient is applied across the vessel so that condensation is inhibited from forming on the interior surface of the barrier, thus permitting clear illumination of the sample for visual imaging, fluorescence studies and light scattering detection.

Abstract: A method and apparatus are disclosed which enable the reduction of sample carryover in the measurement cell of an analytical instrument. A sample cell is defined as a region sealed within a first o-ring. Located outside of said sample region is another o-ring which seals and defines a seal wash region as the region between the first and second o-ring. After the fluid sample is injected into the measurement cell a pressure is applied to the seal wash region, forcing the first o-ring to the innermost extent of the groove in which it sits, expelling any trapped solvent and removing from the measurement cell a significant dead volume while the cell is flushed and prepared for a new sample and corresponding measurement.

Abstract: A method for measuring the physical properties of a drug formulation suspended in a pressurized liquid propellant and a system to enable such measurements is disclosed. Drug formulations suspended in pressurized liquid propellant used in Pressurized Metered Dose Inhalers (pMDIs) are propelled in their native liquid state into an analytical instrument with a measurement cell capable of withstanding the pressure required to retain the sample in liquid form by employing a device to rapidly release the contents of the pMDI canister into the measurement instrument wherein the sample's electrophoretic mobility and size may be determined by MP-PALS or other techniques. A series of valves permits the maintenance of the high pressure in the system. Once the measurements are made, the pressurized liquid is allowed to pass to waste or another analytical instrument by opening an exit valve.

Abstract: A method and apparatus are disclosed for the collection of light scattered from a liquid sample contained within a multiwell plate for which evaporation from the wells is mitigated by the application of a barrier between the liquid sample and the environment. A vertical thermal gradient is applied across the vessel so that condensation is inhibited from forming on the interior surface of the barrier, thus permitting clear illumination of the sample for visual imaging, fluorescence studies and light scattering detection.

Abstract: A method and apparatus are disclosed for the collection of light scattered from a liquid sample contained within a multiwell plate for which evaporation from the wells is mitigated by the application of a barrier between the liquid sample and the environment. A vertical thermal gradient is applied across the vessel so that condensation is inhibited from forming on the interior surface of the barrier, thus permitting clear illumination of the sample for visual imaging, fluorescence studies and light scattering detection.

Abstract: An electrode for use in instruments capable of measuring the electrophoretic mobility of particles in solution is disclosed. The electrode is comprised of an inexpensive support member, generally made of titanium, onto a flat surface of which has been connected, generally by microwelding, a flat electrically conductive but chemically inert foil member, preferably platinum. A uniform texture can be generated on the exposed surfaces of the electrode by various means including tumbling the electrode with an abrasive. An oxide layer can be generated on the support member by soaking the composite electrode in an appropriate medium, protecting the exposed surface of the support member from fluid contact with the sample solution, while the foil member, unaffected by the oxidation process, is able to contact the sample solution.

Abstract: An electrode for use in instruments capable of measuring the electrophoretic mobility of particles in solution is disclosed. The electrode is comprised of an inexpensive support member, generally made of titanium, onto a flat surface of which has been connected, generally by microwelding, a flat electrically conductive but chemically inert foil member, preferably platinum. A uniform texture can be generated on the exposed surfaces of the electrode by various means including tumbling the electrode with an abrasive. An oxide layer can be generated on the support member by soaking the composite electrode in an appropriate medium, protecting the exposed surface of the support member from fluid contact with the sample solution, while the foil member, unaffected by the oxidation process, is able to contact the sample solution.

Abstract: One or more homogenizing elements are employed in a flow through, multi-detector optical measurement system. The homogenizing elements correct for problems common to multi-detector flow-through systems such as peak tailing and non-uniform sample profile within the measurement cell. The homogenizing elements include coiled inlet tubing, a flow distributor near the inlet of the cell, and a flow distributor at the outlet of the cell. This homogenization of the sample mimics plug flow within the measurement cell and enables each detector to view the same sample composition in each individual corresponding viewed sample volume. This system is particularly beneficial when performing multiangle light scattering (MALS) measurements of narrow chromatographic peaks such as those produced by ultra-high pressure liquid chromatography (UHPLC).