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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - ULTRACHIRAL (Ultrasensitive chiral detection by signal-reversing cavity polarimetry: applications to in-situ proteomics, single-molecule chirality, HPLC analysis, medical diagnostics, and atmospheric studies)

Teaser

Summary

Chirality plays an essential role in life, providing unique functionalities to a wide range of biomolecules, chemicals, and drugs, which makes chiral sensing important for numerous scientific fields including biology and chemistry and also for the pharmaceutical, cosmetic and food industries. Despite the importance of chiral sensing, its use even today remains limited because chiral signals are very weak to detect. The most widely used techniques for chiral analysis are optical rotatory dispersion (ORD) and circular dichroism (CD). Nonetheless, the obtained signals are typically weak (as small as 10^-5 rad or 10^-7 degrees), requiring long integration times and suffering from imperfect background subtraction procedures.

The objectives of ULTRACHIRAL is to improve the sensitivity of chiroptical sensing, and therefore to expand existing applications of chiral sensing and to explore important new domains which require high sensitivities including: (1) measuring protein structure in-situ, in solution, at surfaces, and within cells and membranes; (2) coupling to high performance liquid chromatography (HPLC) for chiral identification of the components of complex mixtures; (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.

Work performed

The FORTH group has worked towards finding the best method for measurement of ultrasensitive chiral optical rotation using a ring-cavity-based polarimeter. Three methods were identified in the 1st year, namely the: (a) amplitude modulation method, (b) CW-CCW phase-shift method, and (c) frequency beating method. Preliminary work showed that these methods are not good candidates for achieving the ultrahigh sensitivity goals of ULTRACHIRAL. Therefore, we have devised and implemented a 4th method, named Sideband Phase-Shift (SPS) method, which has recently shown all the qualities needed for ultrasensitive measurements. Overcoming such a large noise source is a huge challenge. In contrast, the SPS method involves beating sidebands of the same beam (CW and CCW separately), and avoids recombination optics and the recombination paths that cause large phase noise.

During the first year, the MAINZ group has developed a system of rotating permanent magnets that can invert the direction of the magnetic field within some seconds. In the second year, the group has moved rapidly towards creating a stand-alone prototype, and they have already demonstrated real-time inline measurements of chiral gasses and chiral gas mixtures using a chiral CRD apparatus. They have demonstrated sensitivities of a few Î¼rad.

The main goal of the EPFL group is (in collaboration with the UOC-MS group) to devise nanophotonic structures that can enhance chiral signals (optical rotation). It is also an interest that these structures have sufficient transparencies which can allow them to be used inside optical cavities (while exhibiting vanishing chiroptical noise). This way, chiral measurements can be enhanced both by the number of passes inside the optical cavity and by the enhancement due to the photonic structures. The initial results on investigation of optical nanostructures for enhancing chiral sensing have been published in the journal ACS photonics [E. Mohammadi et al., ACS photonics 5 2669 (2018)].

The EXETER group is already at a stage where the plasmon-enhanced WGMM detector can detect single chiral molecules (though not yet with strong sensitivity to chirality). Some chiral signatures may be already suggested in their measurements. The UOC-MS group has synthesized polymers with giant Verdet constant (10^3 times larger than fused silica, ~30 time larger than TGG, the magneto-optic material used in the macroscopic cavities). This material is in the process of testing, and the next steps will be to coat one hemisphere of the WGM microresonator and measure the corresponding Faraday splitting, which will be the first measurement of an intracavity Faraday Effect in an WGMM.

The UOXF group has been tasked with developing two cavity-enhanced polarimeters. One of these operates in the near-IR and the other will operate in the mid-IR; both will be used for studies of interfaces and condensed phase samples. The group has already achieved cavity-enhanced pathlengths on the order 10 km at 1335 nm and they are developing a CAD designed holder for the TGG and permanent magnets which allows flipping the magnetic fields. The group is currently working in demonstrating the capabilities of their cavity-enhanced polarimeter using a calcite crystal.

The UOC-MD group has created protocols for the extraction and/or synthesis of chiral standards. They have extracted the chiral compounds Ilicic acid, costic acid, Verbascoside and Forsythoside B. They have measured the optical rotation of these compounds in solution, in various concentrations, using commercial polarimeters, and encountered problems related with the limitations of existing technology.

Plans for the development of new hardware were abandoned, as discussed at the first-year project review meeting, where it was agreed to purchase a newly available commercial device which met performance specifications for WGMM-CCP (WP5) and provides an integrated FPGA for development of analysis code needed for the precommerci

Final results

Currently, the ULTRACHIRAL members have demonstrated chiral sensing without the need for background subtraction or sample removal, with a sensitivity of few microrads, which is already better than comercial instruments. Moreover, members of the consortium have designed novel metamaterial and photonic structures to amplify the optical rotation of a sample placed inside an optical cavity, without compromising the cavity lifetime.
By the end of the project, we anticipate successful combination of optical cavities and metamaterial structures to enhance OR. We also anticipate combining optical rotation with WGMMs and approaching single-molecule sensitivity, as well as combination with HPLC for analytical applications.
A multitude of industries will be benefit by the technologies developed in ULTRACHIRAL, including analytical sensing instrumentation ($48.4 billion), cell analysis ($23 billion), chiral sensing (market value $9.2 billion), protein analysis instrumentation ($10.2 billion) and more.
ULTRACHIRAL aims to using the recent developments in chiral sensing to address important scientific challenges that are currently out of reach. We anticipate high impact in several areas, with emphasis on protein structural studies, medical diagnostics, analytical sensing, cell analysis and ecology.

Most of these objectives are aimed to be completed in Year 4.