Uncle

The Uncle from Unchained Labs is an advanced stability characterization platform that integrates full-spectrum fluorescence, static light scattering (SLS), and dynamic light scattering (DLS) into a single instrument. It enables comprehensive analysis of protein and nanoparticle stability, aggregation, and unfolding, helping researchers optimize formulations and biopharmaceutical development.

Key features and highlights include:

• Minimal Sample Volume: Requires only 9 µL per sample, conserving valuable material.

• Sealed Samples: Your samples are safe from evaporation and can easily be stored for weeks or months for long-term experiments and analyzed again in the same experiment file.

• Multi-Parameter Stability Analysis: Simultaneously measures thermal unfolding (T_m), aggregation onset (T_agg), and particle size in a single experiment.

• High-Throughput Capability: Processes up to 48 samples in one run, enabling efficient screening and optimization.

• Full fluorescence spectrum: Uses intrinsic fluorescence for protein unfolding analysis but also supports dye-based assays with dyes such as SYPRO Orange or SYBR Gold in parallel or alternatively.

• Wide Temperature Range: Supports stability studies from 15°C to 95°C, allowing for precise thermal denaturation analysis.

• Aggregation Monitoring: Detects the formation of aggregates using simultaneous fluorescence and SLS measurements for a complete stability profile.

• Versatile Applications: Ideal for protein formulation, antibody characterization, viral capsid stability, and more.

With Uncle’s automated workflows and powerful analytics, researchers can quickly assess protein stability and make data-driven decisions for biopharmaceutical development.

The Uncle integrates three powerful analytical techniques—fluorescence, static light scattering (SLS), and dynamic light scattering (DLS)—to provide a comprehensive stability profile of biomolecules.

• Fluorescence Spectroscopy: Proteins contain intrinsic fluorophores, such as Trp and Tyr residues, the fluorescence of these amino acids change upon the properties of their local microenvironment. By monitoring fluorescence intensity shifts, Uncle determines the melting temperature (T_m) where proteins begin to denature. Additionally, dye-based assays using SYPRO Orange can be applied to enhance the detection of protein unfolding in cases where intrinsic fluorescence is insufficient. But also dyes binding to DNA can be used to detect the genome ejection from AAV capsids.
• Static Light Scattering (SLS): SLS measures aggregation onset temperature (T_agg) by detecting a change in light scattering due to protein aggregation. This provides insights into formulation stability and aggregation risk.
• Dynamic Light Scattering (DLS): DLS tracks protein size and polydispersity by analyzing fluctuations in scattered light caused by Brownian motion. This method helps identify aggregation and oligomerization trends usually at the beginning and the end of your experiment.

By combining these techniques in a single instrument, Uncle delivers a complete stability profile in one experiment, making it an essential tool for protein and nanoparticle characterization, formulation development, and stability screening.