Miniaturized liquid chromatography focusing on analytical columns and mass spectrometry: A review

The technological advances achieved over the last decades boosted the development of suitable benchtop platforms to work at miniaturized liquid chromatography scale (capillary and nano-LC). Under the right conditions, miniaturized LC can offer higher analysis efficiency resulting in superior chromatographic resolution and overall sensitivity than conventional LC. Among the main advantages are the reduced reagents and sample requirement, the decreasing on analytical column dimensions, and consequently flow rates and the easer coupling to mass spectrometry. This review describes fundamental aspects and advances over miniaturized LC technology with a focus on the last decade. Therefore, relevant characteristics of the most common analytical column, covering both filled (packed and monolithic) and open tubular (PLOT and WCOT) columns, are herein discussed. Alternatively, other modern approaches based on microchip separations or 2D configurations aiming for the sample preparation on the first dimension, are also introduced. Likewise, some positive and negative aspects of these systems over HPLC are underscored. Besides, considering the necessity to developed components to work at capillary or nanoscale, without significant dead-volumes, the most critical features of specially designed instrumentation for benchtop instruments are briefly discussed highlighting connectors, pumping, injections, oven and detection systems. Also, a more detailed section is presented focused on mass spectrometry efforts towards its miniaturization and how this trend can be useful working together with miniaturized LC. Finally, applications of capillary and nano-LC involving bioanalytical, environmental, and food methods are discussed to support the miniaturized LC as a powerful and emergent separation technique for the years ahead.