| Diversity-oriented approach for sensor development is a powerful method in that the large numbers of potential sensor molecules are utilized for multiple sensing tasks. Similar to the natural selection in evolution process, high performance sensors were discovered from varieties of sensor candidate molecules by comparing their selectivity and specificity to the target. Depending on the nature of the sensor, this thesis is divided in two chapters: (1) strategies of a single molecule sensor development for biological application, (2) combinatorial sensing approach to discriminate complex mixtures.;In chapter 1, synthesis of diversity-oriented fluorescence library and systematic library screening methods were investigated as a general sensor discovery strategy. In particular, a favorable fluorescence scaffold, BODIPY was utilized to generate a diversity-oriented fluorescence library. The resulting BODIPY library compounds as well as many other fluorophores were systematically screened to discover a highly selective single molecule sensor in three different platforms: fluorescence live-cell image screening, in vitro emission response screening, and gel-based protein labeling pattern screening. The fluorescence image based screening towards peptide secreting cells identified a live-cell imaging probe for glucagon (BD-105). In parallel, systematic fluorescence profiling in the other two platforms led discoveries of sensors for Zn2+ (BDI-A8), RNA (BDI-A2 ), human serum albumin (BDI-A25) from the in vitro emission screening, and glutathione-s-transferase (F6) from the gel-based protein labeling screening. These examples presented a general applicability of the diversity-oriented fluorescence library approach for single molecule sensor development.;In chapter 2, chemical sensor array comprising various off-the-shelf colorimetric dyes was demonstrated combinatorial sensing strategy to discriminate complex samples. The colorimetric dyes are not necessarily selective for a particular target molecule, but the pattern of combined response from the array is diagnostic fingerprint for the identification. Colorimetric chemical sensor array proved their high discrimination performance by various kinds of metal cations independent to their counter anion. Moreover, complex real-world samples, such as various drinkable waters, were successfully analyzed by the colorimetric sensor array. Cross-reactive dye array permitted the recognition and discrimination of various complex mixture samples, and these results demonstrated practical applicability of the combinatorial sensing approach. |
