This project is about chirality; its importance, its applications, and how we plan to measure it in a robust, sensitive, and versatile manner. So, a few words about chirality, and the basic idea behind this project are due.
Chirality is a fundamental property of life, making chiral sensing and analysis crucial to numerous scientific subfields of biology, chemistry, and medicine, and to the pharmaceutical, chemical, cosmetic, and food industries, constituting a market of 10s of billion €, and growing. Despite the tremendous importance of chiral sensing, its application remains limited, due to the chiral signals typically being very weak. The most widely used techniques for chiral analysis are the optical techniques of optical rotary dispersion (ORD) and circular dichroism (CD). These weak signals (< 10-5 rad) are limited by spurious birefringence and slow and imperfect background subtraction procedures. The poor detection sensitivities of current instruments do not allow important biological and medical processes to be probed, and prevent further understanding and treatment of various diseases.
Recently, the project-coordinating FORTH team has introduced a new form of Chiral-Cavity-based Polarimetry (CCP) for chiral sensing (Sofikitis et al., Nature 514, 76; 2014), which has three groundbreaking advantages compared to commercial instruments: (a) The ORD and CD signals are enhanced by the number of cavity passes (typically ~1000); (b) otherwise limiting birefringent backgrounds are suppressed; (c) rapid signal reversals give absolute polarimetry measurements, not requiring sample removal for a null-sample measurement. Together, these advantages allow improvement in chiral detection sensitivity by 3-6 orders of magnitude.
The aim of ULTRACHIRAL is to revolutionize existing applications of chiral sensing, but also to instigate important new domains which require sensitivities beyond current limits, including: (1) measuring protein structure in-situ, in solution, at surfaces, and within cells and membranes, thus realizing the “holy-grail” of proteomics; (2) coupling to high performance liquid chromatography (HPLC) for chiral identification of the components of complex mixtures, creating new standards for the pharmaceutical, medical, and chemical analysis industries; (3) analysis of chirality in bodily fluids as a diagnostic tool in medicine, drug metabolism and pharmacokinetics; (4) the measurement of the chirality of single molecules, by adapting CCP to microresonators, which have already demonstrated single-molecule detection; and (5) real-time chiral monitoring of terpene emissions from individual trees and forests, as a probe of forest ecology.