Chiral sensing is crucial to many fields, constituting a multibillion Euro industry. The single-pass polarimetric techniques of optical rotation (OR) and circular dichroism (CD) are the most widely-used techniques for the analysis of chiral samples, ranging from the measurement of protein structure, to quality control in the pharmaceutical, chemical, cosmetic, and food industries. However, in general, the OR and CD signals are very small, which place severe constraints on detection sensitivity and time-resolution, limiting the applicablily of chiral sensing.
The idea of improving chiral sensing through the use of optical cavities were developed through the ERC Starting-grant TRICEPS. The obvious idea is that passing through the sample many times (typically of order 1000) can amplify the small chiral signals by this factor, making it easier to measure; however there an obvious problem with this is that background birefringence is also amplified and masks the chiral signal. Through the TRECEPS grant, our group have developed a groundbreaking cavity-based polarimeter with 3 main advantages: (a) The OR and CD signals are enhanced by the number of cavity passes (typically 1000) through a bidirectional 4-mirror bowtie cavity; (b) birefringent backgrounds are suppressed by using a large intracavity magnetic field applied to a low-loss window (producing a Faraday rotation larger than the birefringent backgrounds, which rotationally averages them to be negligible); and (c) reversing the intracavity magnetic field reverses the chiral signals, which gives absolute polarimetry measurements, not requiring the sample to be removed to measure a null sample. These three advantages allow orders-of-magnitude improvements in sensitivity, acquisition time, and sample size, with respect to commercially available polarimeters, and promise to reduce measurement time, sample sizes, and costs in the chiral sensing industry. Demonstration of the cavity enhancement of chiral signals was demonstrated using pulsed lasers [Sofikitis et al. Nature 514, 76 (2014)]. Using pulsed laser made the experiment easy to perform. However, these pulsed lasers are very expensive (between 100-200 kEU) and do not approach the theoretical limits of signal sensitivity (due to pulse fluctations, multimode excitation of the cavity which doesn't allow the bidirectional beams to be aligned antiparallel, and large reflection losses due to the inability of the laser pulses to excite a single cavity mode). Therefore, pulsed lasers are not suited for the development of commercial instruments for chiral detection using chiral enhancement. Such instruments need to be developed using continuous wave (cw) laser and their related technologies.
The main goals of the CHIRALSENSE ERC Proof-of-Concept (PoC) grant were to (a) demonstrate cw-laser-based cavity enhancement of chiral signals, in a form that is compatible with commercial applications (i.e. it uses cw lasers and technology that allows both great experimental sensitivity, but also at an affordable cost, using equipment in the 10-20 kEu cost range), (b) to file a non-provisional patent to provide IPR protection for the first stages of the product development, and (c) to demonstrate and communicate the testing of the working instrument with several companies interested in cavity-based polarimetry (including the application to fields such as HPLC [high-performance liquid chromatography]).
The results of the project are close to the planned outcome: our group has demonstrated world-record sensitivity for chiral optical rotation measurements, based on a cw bow-tie cavity (with absolute measurement of chiral optical rotation with sensitivity better than 10 nrad/pass). We have filed a non-provisional US patent application (on 07-MAY-2015, titled: "CAVITY ENHANCED POLARIMETER AND RELATED METHODS", with application number 14706743).
We have communicated our results by visiting and maintaining close communication with several companies (Accurion, Kaiam, LGR Inc., and PDR-separations), and have used and are using their feedback for further development, with the goal of demonstrating the feasibility of a compact and cost-effective product.
