Publication Highlights – 2024

Introduction

As 2024 comes to an end, it's the perfect time to reflect on what an extraordinary year it has been for light scattering research. The broader light scattering community has made significant contributions, with over 1,400 publications citing Wyatt instruments this year.

In the spirit of celebrating these achievements, we’ve chosen to spotlight a few publications. We’ll summarize nine journal articles, and share insights on trends observed. If any of these summaries catch your eye, there’s no better way to explore than by diving into the original papers!

Polymer characterization

Topic: Polymer, SEC-MALS
Light Scattering Instruments: DAWN™ MALS detector, Optilab™ dRI detector

In the field of polymer research, three publications were selected including content appropriate for either both newcomers curious about multi-angle light scattering (MALS) and experienced users.

The first study serves as both a tutorial and a review on polymer characterization via size-exclusion chromatography with multi-angle light scattering (SEC-MALS). This review article, written by the Matson and Schulz groups at Virginia Tech, is an excellent entry point for polymer scientists interested in SEC-MALS. The article covers theory, experimental considerations, data analysis, and troubleshooting. There’s even a helpful section addressing six common misconceptions about multi-angle light scattering, making it a worthwhile read for anyone.

Matson, John B., et al. "Polymer characterization by size-exclusion chromatography with multi-angle light scattering (SEC-MALS): a tutorial review." Polymer Chemistry (2024). https://doi.org/10.1039/D3PY01181J

Next, we have a collaboration between Wyatt Technology and USP, focused on PLGA characterization. The team developed a method to ensure consistent molecular weight determination across different PLGA batches using SEC-MALS. The study delves into aspects like column selection, baseline definition, and peak selection. Those working directly with PLGA will find the discussion valuable, but the approaches and considerations outlined offer insights that can benefit the broader polymer community. While the first publication is more of an entry-level resource, this one is a deeper dive, ideal for scientists familiar with SEC-MALS who are looking to implement this method in a routine and regulated testing environment.

Ren, Yixin, et al. "USP’s Characterization of Commercial Poly (lactic-co-glycolic acid) Utilizing SEC-Multi-Angle Light Scattering and Refractive Index Techniques via Absolute Method Approach." Journal of Pharmaceutical and Biomedical Analysis Open (2024): 100031. https://doi.org/10.1016/j.jpbao.2024.100031

Lastly, there is a collaboration between the Fraunhofer Institute and Chevron Phillips Chemical, presenting a comparative study on low-density polyethylene (LDPE) using multiple characterization techniques—SEC-MALS, AF4-MALS, HT-HPLC, and 2D-LC. This paper provides insights into LDPE samples produced using various reactor technologies, exploring how these methods reveal details about molar mass distribution and long- and short-chain branching. The authors discuss and compare the insights gained from these different analytical techniques.

Arndt, Jan-Hendrik, et al. "Low-Density Polyethylene–New insights into an old material under comparative studies using SEC-MALS, AF4-MALS, HT-HPLC and 2D-LC." Polymer 290 (2024): 126582. https://doi.org/10.1016/j.polymer.2023.126582

These three studies underscore the versatility of multi-angle light scattering (MALS) in polymer research. From foundational tutorials and practical guidance to advanced method development and comparative analyses, MALS proves essential for a range of applications in polymer characterization.

Inorganic nanoparticles and evaporative deposition

Topic: Nanoparticles, DLS, SLS, ELS
Light Scattering Instruments: DynaPro™ ZetaStar™ DLS, SLS, ELS instrument

This set of studies focuses on manufacturing, particularly the printing and evaporative deposition of nanoparticles. In this field, particle size and zeta potential are crucial for ensuring the colloidal stability of nanoparticles. At the nanoscale, size influences their function—whether in plasmonic resonance properties, electronic band structure, or even magnetic behavior. To maintain particle stability in solution, adjusting the surface charge is important. A common approach is to modify the storage solution to optimize the zeta potential, either positively or negatively, creating a net repulsive force between particles, which reduces flocculation and sedimentation.

The first study highlights a freestanding monolayer of CrOCl created via chemical exfoliation. CrOCl has gained attention in the field of 2D materials due to its complex magnetic properties in bulk form. Researchers at Princeton University chemically exfoliated CrOCl using organolithium reagent lithiation, achieving stable nanosheets with a zeta potential around -17 mV. This work is particularly intriguing because of the unique characteristics of the material and the changes observed between its bulk and exfoliated forms.

Villalpando, Graciela, et al. "Freestanding monolayer CrOCl through chemical exfoliation." Nanoscale Horizons 9.10 (2024): 1766-1773. https://doi.org/10.1039/D4NH00137K

The second study, from the Max Planck Institute, focuses on creating intricate micro- and nanoscaffolds for high-uniformity 3D microstructures with substantial mass loading. They fine-tuned the zeta potential, lowering it to around -5 mV, which minimized electrostatic repulsion so particles remained stable in solution but formed coatings as the solution dried. By refining a dip-coating method with capillary trapping, they were able to work with various materials—polymers, metals, and metal oxides—and produce complex 3D structures.

Lyu, Xianglong, et al. "Capillary trapping of various nanomaterials on additively manufactured scaffolds for 3D micro-/nanofabrication." Nature Communications 15.1 (2024): 6693. https://doi.org/10.1038/s41467-024-51086-2

The third paper, a large collaborative effort among six universities and the U.S. Air Force Research Laboratory (including the University of Utah, Sungkyunkwan University, Georgia Tech, the University at Buffalo, and Brown University), combines mathematical modeling, simulations, and custom-engineered devices. The team created a model and experimental setup to test how factors such as particle size, charge, flow rate, and temperature affect particle migration during evaporative deposition. One interesting aspect is the team’s hypothesis that atmospheric CO₂ absorption changes the local ionic strength at the evaporative interface, impacting particle distribution. Such extensive collaboration is rare, and this work holds significant potential for advancing large-scale manufacturing processes.

Ghosh, Samannoy, et al. "Diffusiophoresis-enhanced particle deposition for additive manufacturing." MRS communications 13.6 (2023): 1053-1062. https://doi.org/10.1557/s43579-023-00432-4

Altogether, these studies illustrate the importance of zeta potential—and how Wyatt instruments contribute—to stabilizing inorganic nanoparticles in solution for effective additive manufacturing.

Lipid Nanoparticles characterization

Topic: mRNA, LNP
Light Scattering Instruments: Eclipse™ FFF system, DAWN MALS detector, Optilab dRI detector

The first publication completed by the team at Regeneron investigates mRNA degradation using a suite of chromatographic methods, including SEC-MALS. This study is classifed as “LNP-related” because mRNA is among the most common LNP payloads. Traditional SEC separation can be difficult for mRNA due to its size and the team tackles that problem by using a ultrawide- pore column to achieve separation. The method was designed to be simple and easily implemented for routine analysis. A link to the publication can be found below. Additionally, Jacklyn Cika, one of the paper's authors, has presented this work in a webinar with Wyatt Technology for those interested in further details.

Dayeh, Daniel M., et al. "Comprehensive chromatographic assessment of forced degraded in vitro transcribed mRNA." Journal of Chromatography A 1722 (2024): 464885. https://doi.org/10.1016/j.chroma.2024.464885

View Webinar

The next two publications from Genentech focus on LNP payload quantification, encapsulation, and morphology analysis using FFF-MALS. LNPs are typically large, which presents two major challenges: they’re difficult to separate using standard SEC methods, and their intrinsic particle scattering complicates payload quantification. FFF separation resolves the separation issue, and the LNP analysis module within ASTRA software addresses both challenges.

The first study delves into the development of a separation method using FFF-MALS, validating results, and achieving a remarkable outcome: in a single injection, they could determine encapsulation efficiency, obtain high-resolution sizing, and assess payload distribution by size. The second study takes a different approach, focusing on morphology. By leveraging the rms (radius-to-molar-mass) relationship, they distinguished between spherical particles and lipodisks, providing critical insights into particle structure. Towards the end of the publication, the author hints at further analysis of bleb structures – hopefully, updates will be available soon. The team anticipates that these methods could support both formulation development and process control in LNP research.

Gao, Ziting, et al. "Development of an advanced separation and characterization platform for mRNA and lipid nanoparticles using multi-detector asymmetrical flow field-flow fractionation." Analytical and Bioanalytical Chemistry 416.24 (2024): 5281-5293. https://doi.org/10.1007/s00216-024-05455-x

Tang, Shijia, et al. "Scaling laws for nanoparticles–Online shape heterogeneity analysis by size exclusion chromatography coupled with multi-angle light scattering." Journal of Chromatography A 1736 (2024): 465386. https://doi.org/10.1016/j.chroma.2024.465386

These publications also reflect a shift in LNP analysis trends, moving from traditional bulk/unfractionated analysis to more detailed characterization that not only quantifies the encapsulated payload but also determines if the payload is distributed in the intended particle sizes. Together, these three papers offer a strong foundation for researchers aiming to use SEC and FFF-MALS to establish methods for high-resolution LNP sizing and payload distribution analysis.

Share your work with us!

Keeping up with so many advancements can be challenging and we are especially grateful to friends, colleagues, and dedicated Wyatt instrument users who have shared their work with us.

If you come across an interesting publication, please don’t hesitate to send it our way. Let’s continue building our community of knowledge and discovery together!

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