Fluorescent Phenotyping of Blood Cells Using a Differential Sensing Strategy: Differentiating Physiological Aging Stages and Neuro-Degenerative Disease Drugs

Abstract

Blood continually contributes to the maintenance of homeostasis of the body and contains information regarding the health state of an individual. However, current hematological analyses predominantly rely on a limited number of CD markers and morphological analysis. In this work, differentially sensitive fluorescent compounds based on TCF scaffolds are introduced that are designed for fluorescent phenotyping of blood. Depending on their structures, TCF compounds displayed varied responses to reactive oxygen species, biothiols, redox-related biomolecules, and hemoglobin, which are the primary influential factors within blood. Contrary to conventional CD marker-based analysis, this unbiased fluorescent phenotyping method produces diverse fingerprints of the health state. Precise discrimination of blood samples from 37 mice was demonstrated based on their developmental stages, ranging from 10 to 19 weeks of age. Additionally, this fluorescent phenotyping method enabled the differentiation between drugs with distinct targets, serving as a simple yet potent tool for pharmacological analysis to understand the mode of action of various drugs. A differential sensing approach is demonstrated to distinguish distinct aging status of mouse using TCF probes. Despite there is no reliable CD markers selective for aging progress, cross-reactivity of TCF probes generates unique fingerprint of aging by blood cell analysis.image