| The first consideration in any analytical measurement is sample preparation. In many measurements, it is only when this step has been precisely optimized that one can obtain data of decent quality. Here I will describe some details of the chemistry and physics involved in creating a sample, or an array of many samples, and how those samples change or evolve with time, depending of their composition and surroundings. This dissertation presents advancements in droplet-based microfluidic technologies for initial sample concentration as well as a microfluidic device that digitizes a sample into an array of discrete volumes. In addition, the mechanism of analyte incorporation into matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) matrix crystals will be discussed. Polymorphs of MALDI matrix 2,5-dihydroxybenzoic acid (2,5-DHB) crystallize concomitantly and were selected as a model system to study the role of the matrix in the MALDI measurement. In an exploitation of the high surface area to volume ratio in a microfluidic system, aqueous samples were concentrated by forming a continuous stream of sample droplets in an immiscible phase within which water is very slightly soluble. Heating was found to amplify this effect.A microfluidic device was developed that digitizes samples into an array. The device is based on an inherent fluidic phenomenon, where an incoming aqueous sample divides itself into an array of chambers that have been primed with an immiscible phase. Self-digitization of sample volumes results from the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the digitized samples in the chambers. This device can partition and retain 100% of a sample. Once formed, additional reagents can be added to the discretized samples or a specific sample can be removed for downstream analysis. Physical parameters governing the behavior of this device have been characterized experimentally and using simulations. The final volume of the discretized sample at each location is defined by the geometry and size of each chamber. Thus, we can form an array of samples with varying but predefined volumes. This feature was exploited to separate the growth of otherwise concomitant polymorphs from a single solution. |
