An increasingly complex landscape of antigen targets and therapeutic modalities demands the coordinated use of advanced tools for robust characterization. We present an integrated toolkit for biophysical characterization to support the discovery and development of novel biotherapeutics and genetic medicines. By combining light-scattering techniques with single-particle analysis, we deliver deep insights and drive innovation across antibody-antigen, lipid-nanoparticle, and virus-like particle platforms.

The heterogeneity of mRNA lipid nanoparticles (LNPs) must be taken into account in order to rigorously correlate microscopic biophysical properties to therapeutic function (ACS Nano, 2026). For the first time, we demonstrate an in-solution, all-optical, high-throughput method to measure LNP size, mRNA payload, interaction kinetics, and intraparticle structure (how mRNA is arranged) of vaccine nanoparticles as a function of formulation parameters, in correlation with cryo-electron microscopy of these particles.

R CE-SDS analysis of a novel biologic product using BME reported a surprisingly higher level of HMW than native SEC and NR CE-SDS. Further investigation revealed that these HMW species were BME-induced artifacts, with their abundance strongly dependent on BME concentration. By evaluating alternative reducing agents via a variety of analytical characterizations, post-reduction alkylation has been identified as a key step to eliminate these artifacts and enable accurate quantification.

Analytical methods continue to evolve rapidly to meet the evolving needs of new therapeutic modalities. Emerging analytical platforms often utilize different measurement principles, making direct comparison difficult and leading to lack of concordance.  Bridging between methods requires comparative studies and a well characterized reference material or control. This talk will outline considerations for design and analysis of such studies using case studies from the mAb and AAV gene therapy fields.

In our under-review work, we demonstrate that resting CD8 T cells exhibit a bimodal buoyant-mass distribution—measured label-free by a Suspended Microchannel Resonator (SMR)—that defines an intrinsic immune-fitness axis. This rapid, <20-minute assay accurately stratified checkpoint-therapy response in a neoadjuvant melanoma cohort (AUC 0.88), outperforming tumor mutational burden. Mechanistically, "light" cells are exhaustion-prone, while "heavy" cells are biosynthetically primed, offering a novel phenotypic readout for drug discovery and clinical stratification.

Novel biologic modalities introduce new analytical challenges that require flexible and carefully designed characterization strategies. This presentation will discuss how fit-for-purpose analytical approaches can be applied to enable comprehensive assessment of emerging therapeutic formats. Topics will include selecting appropriate analytical techniques, aligning characterization depth with development phase, and leveraging complementary methods to build a robust understanding of molecular attributes that influence quality, stability, and biological activity.

Early identification of chemical liabilities is essential for advancing developable biologic candidates without delaying timelines. We present a high-throughput MS screening platform that overcomes peptide mapping bottlenecks through an innovative acquisition strategy and automated data processing, delivering a 100-fold increase in throughput. This workflow enables early, comprehensive PTM characterization and generates high-density datasets to support ML/AI-driven antibody engineering.

Sodium dodecyl sulfate capillary electrophoresis (CE-SDS) and capillary isoelectric focusing (cIEF) are two primary biochemical assays that provide information on purity (CE-SDS) and charge distribution (cIEF-UV/MS) of protein therapeutics. Subunit digests of therapeutic antibodies which cut above and below the hinge can provide further insight into product purity and location of post-translational modifications (PTMs). The subject of this research was to develop procedures for the analysis of enzymatic digests of mono- and bispecific antibodies using both CE-SDS and cIEF-UV/MS for identification and localization of post-translational modifications. Analyzing subunit digests alongside native samples by CE-SDS may help to identify "unknown" peaks such as aglycosylated species, heavy-heavy-light, half-mAb, etc. Analyzing subunit digests by cIEF-UV/MS can identify enzymatic versus non-enzymatic PTMs and may help localize these modifications to specific regions of the molecule (HC, LC, Fab, Fc, etc.). The workflow developed in this study may provide more insight into the localization of PTMs and the overall purity of a molecule.

Alpha-gal epitopes on glycolipids and glycoproteins are central to Alpha-Gal Syndrome (AGS), yet their distribution in experimental reagents is poorly defined. We performed LC–FLR–MS glycome profiling of rabbit red-blood cells, developing a unified glycan-release workflow to quantify alpha-gal across glycolipids and N-linked glycoproteins. Over 64% of alpha-gal–containing glycans originated from glycolipids, with 2.24-fold higher mass-spectrometric responses, establishing glycolipids as the predominant alpha-gal source.

Comprehensive analysis of glycosylation is essential for biologic characterization but remains analytical challenging due to microheterogeneity and low abundance of glycopeptides. This presentation introduces an online enrichment approach that integrates with LC–MS workflows for glycopeptide mapping and glycoproteomics. The discussion will focus on how this new method increases analytical sensitivity, expands glycopeptide coverage, and enables more efficient characterization of glycosylation profiles in therapeutic proteins and other complex matrices.

Characterization of drug substance and drug product is a critical component of mRNA vaccine development and manufacturing. Traditionally, in-process and release testing has relied heavily on manual methods, which can limit throughput and introduce analyst-to-analyst variability. To address these challenges, we developed and implemented automated versions of two key assays: a dsRNA ELISA for quantifying dsRNA impurities, and a RiboGreen assay for assessing mRNA content and encapsulation efficiency. Both automated assays demonstrated strong concordance with their manual counterparts while offering substantial improvements in throughput and reproducibility.

Traditional analytical methods often struggle to capture the mRNA degradation with sufficient resolution. This study explores direct nanopore sequencing as a high-resolution method for monitoring mRNA integrity in solution. By enabling direct, long-read characterisation, the approach provides deeper insights into the preferred “hot spots” for degradation. The results demonstrate how nanopore technology can be applied for the design and development of robust mRNA-based therapeutics.

Accurate concentration determination is a critical enabler across biological drug development and the full product lifecycle. This study benchmarks slope spectroscopy (UV SoloVPE) against orthogonal Protein A affinity chromatography, focusing on method variability and bias. Statistical analysis shows markedly lower variability and significantly faster turnaround for slope spectroscopy. These performance gains deliver higher accuracy and faster reporting, positioning slope spectroscopy as a compelling technology for routine concentration determination.

We recently developed an automated, ultra-sensitive nHDX-MS platform that transforms HDX from a late-stage validation method into a high-throughput screening tool. Operating at femtomole-level sensitivity, the platform enables structural characterization of challenging targets for which low protein yields have historically hindered analysis. Our automated pipeline supports epitope mapping and ligand screening at unprecedented speeds with minimal material consumption, offering a scalable solution for protein systems with limited sample availability. This high-throughput screening enables characterization of up to 96 interactions per day, has sufficient sensitivity for weak binders (µM range), and is applicable to structural analysis of membrane proteins and transcription factors