Abstract: Embodiments described herein relate to improved devices and techniques for improving the calibration of laboratory analytical instruments, especially those whose detector response generally exhibit a non-linear response curve. Some embodiments relate to applying a relatively high voltage at the central pin of a charged aerosol detector's (CAD's) ion trap. By applying a high voltage, relatively more small particles (which generally constitute background reagents) are driven into the ion trap's outer wall, thus improving the CAD's signal-to-noise ratio. Other embodiments, which may be used separately or together with the increased voltage, use calibration standards data and the best-fitting model from a variety of fitting models (which are not limited to a power law function) to transform the raw non-linear data points to linear data points. Consequently, a best linear fit calibration line can be obtained for each individual analyte using the transformation model most appropriate to that analyte.

Abstract: The present technology provides methods for increasing sensitivity of detection and/or quantification of a negatively charged analyte, e.g., an oligonucleotide, using an analytical system that comprises liquid chromatography and mass spectrometry. The methods comprise passing an acidic solution through the analytical system, i.e., through a fluidic path from the mobile phase reservoir to the detector to remove or displace, at least in part, metal ions adsorbed to charged sites in the fluidic path.

Abstract: The present technology provides methods for increasing sensitivity of detection and/or quantification of a negatively charged analyte, e.g., an oligonucleotide, using an analytical system that comprises liquid chromatography and mass spectrometry. The methods comprise passing an acidic solution through the analytical system, i.e., through a fluidic path from the mobile phase reservoir to the detector to remove or displace, at least in part, metal ions adsorbed to charged sites in the fluidic path.

Abstract: A self-assembled engineered lattice of nanometer-scale silica particles, or other suitable particles generally resembling regularly-sized spheres, is configured in a separation bed for electrophoresis, isoelectric focusing, chromatography, or other voltage-induced separation of analytes. After separation, the analytes are immobilized on the separation bed and then ionized using matrix-assisted laser desorption/ionization (MALDI) for use with a mass spectrometer. The nanoparticles can be coated with polymers that activate to immobilize the analytes or assist with MALDI. The separation can occur in two dimensions.

Abstract: A self-assembled engineered lattice of nanometer-scale silica particles, or other suitable particles generally resembling regularly-sized spheres, is configured in a separation bed for electrophoresis, isoelectric focusing, chromatography, or other voltage-induced separation of analytes. After separation, the analytes are immobilized on the separation bed and then ionized using matrix-assisted laser desorption/ionization (MALDI) for use with a mass spectrometer. The nanoparticles can be coated with polymers that activate to immobilize the analytes or assist with MALDI. The separation can occur in two dimensions.