DEVELOPMENT OF OPTICAL SENSOR BASED ON COLORIMETRIC DYE ARRAY AND DIVERSITY ORIENTED FLUORESCENCE LIBRARY APPROACH

Abstract

The development of novel optical sensors has recently received considerable interest due to their adaptability in the imaging applications in diagnostics and medical researches. Depending on the nature of the optical sensors this thesis is consisted of three main chapters: (a) strategies of single molecule sensor development for biological application, (b) strategies of combined fluorescent molecules (i.e. FRET) based sensor development and (c) combinatorial sensing approach to discriminate highly cross reactive analytes. In the first part of the thesis, synthesis and evaluation of the photo physical properties of two diversity-oriented fluorescent xanthone libraries (CX and AX) are explored. A solid phase methodology is successfully utilised for further diversification of the CX and AX compounds to their corresponding derivatives (CXAC, CXCA and AXAC, AXCA). By high throughput screening of CX derivatives against mouse embryonic stem cells, one compound CXAC 59 (CDb8) was discovered, that selectively stained with mESC over MEF and other differentiated cells. In the next Chapter, synthesis of FRET based fluorescent libraries are demonstrated. Here, CX and AX compounds were coupled with suitable green and yellow emitting fluorescence BODIPY dyes to generate their corresponding FRET libraries - CXBD, AXBD and AXBY which display average energy transfer efficiency of 95% from xanthone (donor) to BODIPY (acceptor). In the following chapter, the sensing paradigm is shifted from selective detection to the discrimination of analytes. Here, the concept of combinatorial sensing strategy has been successfully utilized to develop an artificial tongue by using pH indicators and boronic acid ensemble array for the quantitative discrimination of three different sugars- glucose, fructose and sucrose.