Aura PTx System

Aura PTx System — Technical and Application Summary

Significance of the topic

The characterization of low-volume biologic formulations and reliable identification and quantitation of subvisible particles and degraded excipients (notably polysorbates) are critical for biotherapeutic product quality, stability, and safety. Rapid, high-throughput techniques that distinguish proteinaceous aggregates from non-protein particulate contaminants and quantify excipient degradation enable formulation screening, trouble‑shooting of stability failures, and support regulatory release testing while minimizing sample consumption.

Objectives and overview of the system

This specification sheet describes the Aura PTx System, a benchtop platform designed to detect, count, and characterize formulation excipients (including intact and degraded polysorbates) and subvisible particles in protein therapeutics. Key objectives of the system are to:

• Provide fully sampled (100%) imaging of membrane-captured particles with combined brightfield and fluorescence modalities.
• Enable differentiation between proteinaceous and non-protein aggregates without extensive manual image curation or external machine‑learning toolchains.
• Support high-throughput screening with 24‑well or 96‑well membrane plates while using minimal sample volumes.

Methodology

The Aura PTx System integrates three complementary optical modalities:

• Backgrounded membrane imaging (BMI) for high-contrast brightfield imaging of particles captured on membrane filters, providing full-well imaging and complete sampling efficiency.
• Fluorescence membrane microscopy (FMM) using two fluorescence channels to enable selective staining/labeling strategies for distinguishing protein particles from cellular or extrinsic particulates.
• Side illumination membrane imaging (SIMI) which enhances detection of refractive or scattering particles via side-scatter illumination.

These modalities are combined into a workflow that acquires brightfield and fluorescence images without the need for instrument cleaning between measurements, supporting continuous high-throughput operation.

Used instrumentation

Key instrument specifications and operational features provided in the product sheet:

• Imaging area: 24.6 mm2 per field (full-well imaging modality).
• Optics: 4× objective; resolution ~1.0 pixel/µm.
• Sampling efficiency: 100% (full-well capture on membrane).
• Illumination:
  • Brightfield LED: 455 nm
  • Side-scatter (SIMI) LED: 465 nm
  • Two fluorescence channels: Channel 1 Ex 440 nm / Em 500 nm; Channel 2 Ex 482 nm / Em 524 nm
• Detectable particle size range: effectively from >1 µm up to <5 mm equivalent circular diameter (ECD).
• Minimum sample volume: as low as 5 µL depending on assay design.
• Read times: Brightfield (BMI) ~1 minute per sample; Fluorescence (FMM) ~30 seconds per sample.
• Sample formats: 24‑well or 96‑well filter membrane plates; membrane types include white polycarbonate for brightfield and black polycarbonate for fluorescence assays.
• Software: Particle Vue 5.x suite for image acquisition and analysis; Windows OS; robotic compatibility for automation.
• Physical and electrical: universal input 90–265 Vac; instrument dimensions ~13.5 × 18 × 13 in; weight ~57 lbs.

Main capabilities and performance (results summary)

Although this is a product specification rather than an experimental report, the sheet documents practical performance characteristics relevant to users:

• Full‑well imaging and 100% sampling efficiency reduce statistical uncertainty associated with subsampling and filter heterogeneity.
• Dual fluorescence channels permit multiplexed staining strategies for confident classification of protein versus non-protein particles and detection of excipient degradation products when appropriate probes are used.
• Low minimum sample volume (≥5 µL) supports studies where material is limited (formulation scouting, early discovery, stability sampling).
• Rapid per‑well read times (≈1.5 minutes combined BF+FL) make high‑throughput screening of 96‑well plates feasible within practical timeframes.
• Side scatter illumination and BMI increase sensitivity to small, low‑contrast particles often missed by standard brightfield imaging alone; effective detection limit cited as >1 µm ECD.

Benefits and practical applications

The system targets formulation scientists, QC/QA labs, and analytical groups working on biotherapeutics. Practical advantages include:

• Accelerated formulation development: enables design-of-experiments (DoE) workflows with rapid screening of excipient combinations and stress conditions.
• Polysorbate degradation monitoring: provides a route to detect and quantify polysorbate-derived particles and degraded products alongside protein aggregates.
• Aggregate identification: straightforward out‑of‑the‑box discrimination between proteinaceous and non-protein particulates reduces manual review time and improves confidence for root-cause analysis.
• Low sample consumption and compatibility with automation make the platform suitable for early‑stage material‑limited studies and integration into high‑throughput labs.
• Regulatory support: standardized imaging, full‑well sampling, and software-controlled analysis aid traceability and method reproducibility for stability and release testing.

Future trends and potential developments

Possible directions to extend the platform's utility include:

• Expanded fluorescence capability (additional spectral channels) and validated fluorescent probes to target specific excipient degradation products or post-translational modifications.
• Embedded machine‑learning classifiers trained on curated datasets to further automate particle classification and reduce remaining manual oversight.
• Integration with LIMS and automated liquid-handling/robotics for end-to-end high-throughput workflows and sample traceability.
• Higher resolution optics or complementary modalities (e.g., Raman, hyperspectral imaging) for chemical fingerprinting of particles without extraction.
• Method validation packages and robustness studies to accelerate regulatory acceptance for QC release assays.

Conclusion

The Aura PTx System combines full-well backgrounded membrane imaging, dual-channel fluorescence membrane microscopy, and side-illumination scatter imaging into a compact, high‑throughput platform for characterizing particles and excipient degradation in biologic formulations. Its low sample volume requirements, 100% sampling efficiency, rapid read times, and software-driven analysis address common bottlenecks in formulation development and stability testing, making it a practical tool for laboratories focused on protein therapeutic quality and safety.

References

Waters Corporation. Aura PTx System specification sheet. Milford, MA, Waters Corporation; 2025. October 25-14668 720009104EN REV. C. Waters Corporation, 34 Maple Street, Milford, MA 01757 U.S.A.