Annual Review 2024-2025

Ending the cold chain: novel hydrogel set to improve access to vital medicines The storage and distribution of vital protein therapeutics presents several complex challenges. Many medicines and vaccines need stable, temperature-controlled environments and chemical additives such as preservatives to keep them effective and safe for use. This requires cold storage infrastructure and reliable energy sources which causes accessibility and affordability challenges, especially in developing countries where resources are limited. A multidisciplinary team led by a team of researchers from the University of Glasgow have designed the world’s first hydrogel technology for the storage and distribution of crucial medicines and other biopharmaceuticals without the need for refrigeration or chemical additives. The new hydrogel system has been designed to stabilise proteins, protecting their properties and functionality under stresses such as vibration and temperatures as high as 50 degrees centigrade. Key to this breakthrough is the hydrogel’s mechanical structure. The unique gel was developed using a Low Molecular Weight Gelator (LMWG) and a chemical trigger that prompts the gelator molecules to self-assemble into very long, three dimensional fibres. When the proteins are added, they become lodged in the spaces between the fibres, where they are unable to mix and aggregate. During the initial stages of the research the gels were explored with time-resolved experiments on Diamond’s beamline I22 using small angle X-ray scattering (SAXS) techniques. The resulting scattering patterns revealed several structural parameters in the gels, which were then analysed using mathematical models. Further experiments were conducted at Diamond’s B21 beamline to confirm that the protein which entered the gel was the same after it was expressed. With a patent-pending, different market segments are being explored where the novel hydrogels can make impact, including vaccines for low-resource environments, therapeutic proteins and enzymes, and antibody therapies. DOI: 10.1038/s41586-024-07580-0 A N N U A L R E V I E W 2 0 2 4 / 2 5 S O F T C O N D E N S E D M AT T E R G R O U P 26 Initial gel studies. SAXS patterns of gels made in presence of calcium chloride (black) and without CaCl2 (red). The fits obtained through model fitting are overlayed on each spectrum. The plotted data show the averaged scattering pattern obtained from five measurements across the sample. Q (A -1 ) Intensity (A.U.) A B21 Sample Environment Unit (SEU) designed by Diamond’s Engineering group. The SEU provides direct heating and cooling of samples from 0 to 150 oC, with an in-line, on axis camera for visualization of the sample. There are added ports for lasers for photo-activation of the sample. In addition, the SEU minimizes air gaps with the sample windows forming the windows with the beamline vacuum system. This unit is optimized for weakly scattering samples. X-rays (from right-to-left) scatter as a cone (purple) whilst the incoming laser light (red) is transmitted through the sample. Modular sample cells (dark grey) can be adapted to hold a variety of sample types (e.g., semi-solids, liquids, gels, solids). The SEU is compatible with geometry for WAXS measurements.