Periodic Reporting for period 1 - CHIRALFORCE (Chiral separation of molecules enabled by enantioselective optical forces in integrated nanophotonic circuits)
Período documentado: 2022-12-01 hasta 2023-11-30
The molecular building blocks of life—such as sugars and amino acids—are of only one-handedness. This broken molecular symmetry has important consequences for bioactive compounds: a molecule of one handedness (i.e. enantiomer) can be an effective medicine while its mirror image is extremely toxic. Consequently, most practical applications demand enantiopure compounds, but most synthesis routes automatically yield a mixture containing both left- and right-handed molecules (typically termed ‘R’ and ‘S’). Separation of enantiomers from mixtures is, therefore, essential, especially in early phase drug discovery processes when many mixtures need to be separated. Current state-of-the-art characterization and separation methods rely on chiral chromatography methods. A major drawback of chromatography techniques is that each mixture of enantiomers requires a customized protocol, which is time-consuming, cumbersome, and extremely costly, becoming a serious roadblock in the agricultural, pharmaceutical, and chemical industries.
CHIRALFORCE aims to revolutionize the field of chiral chemistry by introducing a radically new strategy for separating enantiomers. To enforce this breakthrough, we propose to use chiral optical forces in silicon-based photonic integrated waveguides to separate enantiomers. Supported by theoretical calculations, we propose to reach this ambitious goal by introducing a systematic strategy for separation of enantiomeric molecules via photonic waveguides. Encouragingly, recent studies and experiments show that chiral optical forces are sufficient to achieve enantiomeric separation in nanoparticles.
The overall objective of CHIRALFORCE is to demonstrate enantiomer separation in a compact, on-chip, photonic platform fabricated using standard silicon-based technology. The specific objectives are:
1. Design and synthesize chiral molecules and nanoparticles with response at the wavelengths of interest in the project, which are telecom and visible wavelengths.
2. To establish a general framework of chiral optical forces from molecules to nanoparticles in liquid environments and find the achievable limits in optical near-field design in chiral waveguides.
3. To demonstrate optical transverse and longitudinal spin at cm-scale distances in chiral integrated waveguides at telecom and visible/NIR wavelengths and enantioselective interaction of chiral matter and optical spin.
4. Experimental demonstration of enantiomer separation of nanoparticles, evidencing the ultimate limits of waveguide-based sorting for molecules on silicon-based C-PICs with integrated microfluidics.
CHIRALFORCE aims to revolutionize the field of chiral chemistry by introducing a radically new strategy for separating enantiomers. To enforce this breakthrough, we propose to use chiral optical forces in silicon-based photonic integrated waveguides to separate enantiomers. Supported by theoretical calculations, we propose to reach this ambitious goal by introducing a systematic strategy for separation of enantiomeric molecules via photonic waveguides. Encouragingly, recent studies and experiments show that chiral optical forces are sufficient to achieve enantiomeric separation in nanoparticles.
The overall objective of CHIRALFORCE is to demonstrate enantiomer separation in a compact, on-chip, photonic platform fabricated using standard silicon-based technology. The specific objectives are:
1. Design and synthesize chiral molecules and nanoparticles with response at the wavelengths of interest in the project, which are telecom and visible wavelengths.
2. To establish a general framework of chiral optical forces from molecules to nanoparticles in liquid environments and find the achievable limits in optical near-field design in chiral waveguides.
3. To demonstrate optical transverse and longitudinal spin at cm-scale distances in chiral integrated waveguides at telecom and visible/NIR wavelengths and enantioselective interaction of chiral matter and optical spin.
4. Experimental demonstration of enantiomer separation of nanoparticles, evidencing the ultimate limits of waveguide-based sorting for molecules on silicon-based C-PICs with integrated microfluidics.
WP1: CHIRAL MATTER
The synthesis of Boc-protected racemic amino helicene has successfully been performed. The synthesis was more problematic than described previosly, as a regioisomer was formed in the first synthetic step.A total of 2.6 g racemic Boc-protected amino helicene was synthesized. It was decided to keep the material in this stage as it is believed that the chemical stability of the unprotected amino helicene may not be suitable for long-term storage. Two portions of 150 mg racemic Boc-amino helicene were separated into its enantiomers via preparative SFC. The pure enantiomers and some racemates were shipped to the AMOLF institute for further analyses.
We have also been able to fabricate chiral plasmonic nanocubes showing chiral response - characterized in CD measurements - in the wavelength range between 600 and 800 nm. Such nanocubes are very promising for performing experiments and test on silicon photonic chips.
Using DFT, we have been able to compute the chiral polarizability of some molecules, particularly helicene. We plan to continue working with this method that will enable to link the chemistry (WP1) with the optics (WP2).
WP2: CHIRAL OPTICS
The description of optical forces in the most general case is quite confusing in the literature: different works use different definitions, assumptions, notations, etc. Calculating optical forces reliably was, therefore, a challenge. One of the first aims of CHIRALFORCE was to provide a reliable, clear, and correct expression for optical forces, with all the definitions clearly stated, and all equations carefully derived to ensure consistency with the definitions. A complete and exact description of all optical forces on a dipolar (small) particle was therefore derived and described from first principles, establishing the definitions to be used by all partners in CHIRALFORCE. The results are contrasted with existing literature, highlighting the differences (in terms of definitions, unit systems, prefactors, missing terms, etc.) with each prior work. Our work is, to our knowledge, the only one including all terms of the dipolar force while at the same time providing two alternative (but equivalent) calculation methods: the field-centric approach, and the particle-centric approach.
We applied our equations to two optical systems: cylindrical optical fibers and silicon nitride photonic integrated waveguides. In the case of the waveguides, our study considered force strength and time needed for separating chiral nanoparticles, mainly via quasi-TE guided modes at short wavelengths (405 nm) and the 90°-phase-shifted combination of 14 quasi-TE and quasi-TM modes at longer wavelengths (1310 nm). Particle tracking simulations show successful enantiomer separation within two seconds. These results suggest the feasibility of enantiomeric separation of nanoparticles displaying sufficient chirality using simple silicon photonic integrated circuits, with wavelength selection based on the nanoparticle size.
We also have prepared a full optical set-up to measure the chiral scattering properties of chiral nanoparticles, driven by evanescent fields with superchiral properties.
WP3:Demonstrator of enantioselective separation
A characterization set-up for testing photonic integrated waveguides (wavelengths 1310, 780 and 633 nm) is running. First waveguides and circuits on SiN have been fabricated ad tested. Pressure drop calculations have been performed for various dimensions of microchannels to be integrated on waveguides. Different designs have been made for the waveguide and microfluidics integration (test structures). A process flow has been designed for the fabrication of the test structures using a sacrificial layer approach. Assembly of the first chirality detection platform using JASCO-1500 CD spectrophotometer and modification of its optical path for potential in-line measurement (Detection system v0.1). Testing the chirality measurement capability of this v0.1 with test chemical CSA has been performed.
The synthesis of Boc-protected racemic amino helicene has successfully been performed. The synthesis was more problematic than described previosly, as a regioisomer was formed in the first synthetic step.A total of 2.6 g racemic Boc-protected amino helicene was synthesized. It was decided to keep the material in this stage as it is believed that the chemical stability of the unprotected amino helicene may not be suitable for long-term storage. Two portions of 150 mg racemic Boc-amino helicene were separated into its enantiomers via preparative SFC. The pure enantiomers and some racemates were shipped to the AMOLF institute for further analyses.
We have also been able to fabricate chiral plasmonic nanocubes showing chiral response - characterized in CD measurements - in the wavelength range between 600 and 800 nm. Such nanocubes are very promising for performing experiments and test on silicon photonic chips.
Using DFT, we have been able to compute the chiral polarizability of some molecules, particularly helicene. We plan to continue working with this method that will enable to link the chemistry (WP1) with the optics (WP2).
WP2: CHIRAL OPTICS
The description of optical forces in the most general case is quite confusing in the literature: different works use different definitions, assumptions, notations, etc. Calculating optical forces reliably was, therefore, a challenge. One of the first aims of CHIRALFORCE was to provide a reliable, clear, and correct expression for optical forces, with all the definitions clearly stated, and all equations carefully derived to ensure consistency with the definitions. A complete and exact description of all optical forces on a dipolar (small) particle was therefore derived and described from first principles, establishing the definitions to be used by all partners in CHIRALFORCE. The results are contrasted with existing literature, highlighting the differences (in terms of definitions, unit systems, prefactors, missing terms, etc.) with each prior work. Our work is, to our knowledge, the only one including all terms of the dipolar force while at the same time providing two alternative (but equivalent) calculation methods: the field-centric approach, and the particle-centric approach.
We applied our equations to two optical systems: cylindrical optical fibers and silicon nitride photonic integrated waveguides. In the case of the waveguides, our study considered force strength and time needed for separating chiral nanoparticles, mainly via quasi-TE guided modes at short wavelengths (405 nm) and the 90°-phase-shifted combination of 14 quasi-TE and quasi-TM modes at longer wavelengths (1310 nm). Particle tracking simulations show successful enantiomer separation within two seconds. These results suggest the feasibility of enantiomeric separation of nanoparticles displaying sufficient chirality using simple silicon photonic integrated circuits, with wavelength selection based on the nanoparticle size.
We also have prepared a full optical set-up to measure the chiral scattering properties of chiral nanoparticles, driven by evanescent fields with superchiral properties.
WP3:Demonstrator of enantioselective separation
A characterization set-up for testing photonic integrated waveguides (wavelengths 1310, 780 and 633 nm) is running. First waveguides and circuits on SiN have been fabricated ad tested. Pressure drop calculations have been performed for various dimensions of microchannels to be integrated on waveguides. Different designs have been made for the waveguide and microfluidics integration (test structures). A process flow has been designed for the fabrication of the test structures using a sacrificial layer approach. Assembly of the first chirality detection platform using JASCO-1500 CD spectrophotometer and modification of its optical path for potential in-line measurement (Detection system v0.1). Testing the chirality measurement capability of this v0.1 with test chemical CSA has been performed.
- Ab-initio Calculations of the molecular chiral polarizability of molecules using rt-TDDFT
- Unification of existing approaches used to describe dipolar optical forces and introduces a new symmetry-based ‘force basis’ consisting of twelve vector fields, each weighted by particle-specific coefficients for a streamlined description of force patterns.
- Calculations of chiral forces along SiN waveguides surrounding by fluid show that separation of enantimers with sizes below 100 nm is feasible.
- Unification of existing approaches used to describe dipolar optical forces and introduces a new symmetry-based ‘force basis’ consisting of twelve vector fields, each weighted by particle-specific coefficients for a streamlined description of force patterns.
- Calculations of chiral forces along SiN waveguides surrounding by fluid show that separation of enantimers with sizes below 100 nm is feasible.