Ultrasensitive chiral detection by signal-reversing cavity polarimetry: applications to in-situ proteomics, single-molecule chirality, HPLC analysis, medical diagnostics, and atmospheric studies

the project aims to address the need, both scientific/academic and industrial, for sensitive measurements of chirality, in a variety of contexts. The coordinating Polarization Spectroscopy Group, led by Prof. T. P. Rakitzis at FORTH, has demonstrated a novel way of measuring chirality-induced optical rotation signals. Within the early stages of the project, the demonstrated setup will evolve and mature, becoming more sensitive, robust, and versatile. Once this process reaches a satisfactory stage, a variety of applications will be taken up by the application-oriented members of the consortium, which comprises world-leading groups in their respective fields. The implications of being able to measure chirality sensitively, in a wide range of situations, should have a big impact in a variety of scientific fields and industrial sectors, from analytical chemistry to biology, as well as to the pharmaceutical, cosmetics, food industries, and more. Despite the tremendous importance of chiral sensing, its application remains very limited, as chiroptical signals are typically very weak, preventing important biological and medical applications. Recently, the project-coordinating FORTH team has introduced a new form of Chiral-Cavity-based Polarimetry (CCP) for chiral sensing, which has three groundbreaking advantages compared to commercial instruments: (a) The chiroptical 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 (depending on instrument complexity and price). ULTRACHIRAL aims 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 and chemical analysis industries; (3) chiral analysis of human bodily fluids as a diagnostic tool in medicine; (4) measurement of single-molecule chirality, 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."