Wed, 20.05.2026 PCT patent WO 2025/106389 A1, published May 2025, discloses novel crystalline and cocrystal forms of lutein with improved stability and bioavailability. To our knowledge, it is also the first published patent to contain crystallographic data measured on the ELDICO ED-1.
The patent was filed by a consortium comprising our partner TeraСrystal SRL (Cluj-Napoca, Romania), Iuliu Hațieganu University of Medicine and Pharmacy (Romania), and the Board of Supervisors of Louisiana State University and Agricultural and Mechanical College (USA). The structural characterization at the core of the work was carried out using three-dimensional electron diffraction (3D-ED) on the ED-1 – at room temperature.
Lutein is a xanthophyll carotenoid – a plant pigment with a sequence of ten conjugated carbon-carbon double bonds. It accumulates in the inner retinal layer of the human macula, where it absorbs short-wavelength blue light and acts as a primary antioxidant. There is consistent evidence linking dietary lutein intake to reduced risk of age-related macular degeneration (AMD) and cataracts.
Pharmaceutical exploitation of that protective activity has been constrained by the compound’s physicochemical properties. Lutein is water-insoluble, poorly absorbed in vivo, and – critically for solid-state characterization – chemically fragile. It degrades under light, oxygen, and heat. In practice, it is stored at −20°C to prevent degradation. Growing single crystals of sufficient quality for laboratory X-ray diffraction is extraordinarily difficult: the molecule’s hydrophobic character, sensitivity to oxidation, and slow nucleation kinetics combine to produce only small, poorly-formed crystals.
As a result, prior crystal structure determinations of lutein had only been achieved for solvated forms – structures incorporating ethanol or methanol into the crystal lattice, measured at cryogenic temperatures (113 K). Those solvent interactions alter the molecule’s conformation, causing twisting and bending of the polyene chain that does not reflect the behaviour of pure lutein in its solid pharmaceutical form.
Three-dimensional electron diffraction is the natural tool for this problem. Electrons interact with matter far more strongly than X-rays, which means complete structural datasets can be obtained from nanocrystalline samples orders of magnitude smaller than those required for single-crystal XRD. For a compound that forms small, fragile crystals, this is a practical necessity, not just a technical preference.
The ELDICO ED-1 is a dedicated electron diffractometer – not a repurposed transmission electron microscope – purpose-built for organic and pharmaceutical materials. It operates at low accelerating voltage with a parallel beam, minimising beam-induced damage to sensitive compounds, and its sensitive hybrid-pixel detector captures the weak scattering signals typical of small organic crystals. STEM-mode imaging allows suitable nanocrystals to be identified and centred before data collection begins.
For a material as heterogeneous and fragile as lutein, that combination – controlled illumination, sensitive detection, and the ability to select suitable crystals before committing to a dataset – is what makes the experiment tractable.
Sample preparation was straightforward. A small amount of crystalline lutein powder was gently ground between two glass slides. A carbon-coated 300-mesh copper TEM grid was placed on top of the sample and pressed gently to transfer material. The grid was loaded into the ED-1. An optical microscope confirmed that material had been deposited correctly.
The motorised stage allowed translation and rotation with sub-micrometre precision. Using STEM mode, a suitable nanocrystal was identified and centred in the beam. Diffraction data were collected in 0.5° increments as the crystal was continuously rotated over a 120° range. CrysAlisPro was used for unit cell determination and intensity extraction. The crystal structure was solved with Olex2.