OligoPilot™ Oligonucleotide Synthesizer by Cytiva

Overview

The OligoPilot™ Oligonucleotide Synthesizer is a benchtop-scale, GMP-aligned solid-phase DNA/RNA synthesizer engineered for robust, reproducible synthesis of therapeutic and diagnostic oligonucleotides in the 10–100 mmol range. Designed for early-to-mid-stage clinical development—supporting Phase I/II trial material supply and diagnostic kit manufacturing—the system implements phosphoramidite chemistry under strictly controlled reagent delivery, inert gas purging, and temperature-stabilized coupling environments. Its compact footprint (≤0.8 m²) enables installation within walk-in fume hoods, meeting ISO 14644-1 Class 7 cleanroom-compatible operational requirements when integrated into controlled laboratory environments. The instrument shares core fluidic architecture, valve manifolds, and reactor block design with Cytiva’s industrial-scale OligoProcess™ platform, ensuring intrinsic scalability and process consistency across development and commercial manufacturing scales.

Key Features

• Scalable synthesis capacity: 10–100 mmol per batch, supporting multi-gram to kilogram annual output (≥100 kg/year achievable with trained personnel and optimized SOPs)
• Compact, ATEX Zone 2–certified mechanical design compliant with IEC 60079-10-1 for safe operation in environments with potential explosive atmospheres
• Integrated real-time process monitoring via pressure, flow, and UV-based endpoint detection for coupling efficiency verification
• Single-batch synthesis completion in ≤24 hours, enabled by accelerated phosphoramidite coupling kinetics and optimized deprotection cycles
• UNICORN™ 7.5+ control software platform providing audit-trail-enabled operation, electronic batch records (EBR), and full 21 CFR Part 11 compliance readiness
• Pre-qualified IQ/OQ documentation packages available, including vendor-supplied qualification protocols, test scripts, and executed reports

Sample Compatibility & Compliance

The OligoPilot™ accommodates standard phosphoramidite monomers (DNA, RNA, 2′-O-methyl, LNA, phosphorothioate), universal solid supports (CPG, polystyrene), and common deblocking (trichloroacetic acid) and oxidizing (iodine/water/pyridine) reagents. It supports synthesis of sequences up to 120 nucleotides with high stepwise coupling efficiency (>99.3% avg.) and low deletion error rates. The system complies with ISO 9001:2015 quality management standards and is validated per ASTM E2500-13 (Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems) and ICH Q5A(R2) for impurity profiling. All hardware components—including peristaltic pumps, solenoid valves, and reactor heating elements—are identical to those qualified in OligoProcess™ systems, enabling direct tech transfer and regulatory filing continuity.

Software & Data Management

Controlled exclusively via UNICORN™ software (v7.5 or later), the OligoPilot™ provides deterministic sequence-driven method execution, real-time parameter logging (flow rate, pressure, temperature, reagent volume dispensed), and automated deviation flagging. Data integrity safeguards include user role-based access control (RBAC), electronic signatures, immutable audit trails, and encrypted database storage. Export formats support CSV, PDF eBRs, and XML for integration with LIMS (e.g., LabWare, STARLIMS) and MES platforms. Change control documentation—including impact assessments, revision histories, and version-controlled method archives—is maintained per ICH Q9 and FDA guidance on computerized system validation.

Applications

• Manufacturing of clinical-grade antisense oligonucleotides (ASOs), siRNA, aptamers, and CRISPR guide RNAs
• Rapid prototyping of novel chemistries (e.g., thiomorpholino, PNA hybrids) under GMP-like conditions
• Supply of reference standards and calibration materials for QC testing of large-scale production batches
• Supporting analytical method development (HPLC, MS, CE) through generation of well-characterized oligonucleotide lots
• Bridging preclinical lead optimization to Phase II material supply without re-optimization or re-validation

FAQ

What scale of oligonucleotide synthesis does the OligoPilot™ support?
It delivers 10–100 mmol per synthesis cycle, corresponding to ~3–30 g of crude product depending on sequence length and modification profile.
Is the system compatible with GMP manufacturing environments?
Yes—fully qualified IQ/OQ documentation is provided; software supports 21 CFR Part 11 compliance; hardware meets ISO 14644-1 and ICH Q5A(R2) alignment requirements.
Can synthesis methods be transferred directly to OligoProcess™?
Yes—identical reactor geometry, fluidic pathways, and reagent delivery logic ensure seamless linear scale-up from OligoPilot™ to OligoProcess™ without re-optimization.
Does the system support custom phosphoramidite chemistries?
Yes—open solvent/reagent port configuration and programmable delivery parameters enable integration of non-standard monomers and protecting groups.
What safety certifications apply to the OligoPilot™?
ATEX Zone 2 (gas group IIB, T3), IEC 61000-6-2/-4 EMC immunity/emission compliance, and UL 61010-1 electrical safety certification.