News&Insight

From Small-Volume Samples to Process Scale-Up

Centrifugation is a fundamental step in the preparation of IVD conjugates, yet it can have a direct effect on process consistency. In the manufacture of colloidal-gold and latex-particle conjugates, centrifugation is commonly used for particle recovery, washing, buffer exchange and concentration, and to help remove unbound antibodies and residual reactants. The outcome is governed not by speed alone, but by a validated process window combining relative centrifugal force (RCF), run time, temperature, rotor geometry, and acceleration and deceleration profiles.

Atlas Link Technology operates Eppendorf and Thermo Scientific™ centrifugation platforms across its Design and Development and manufacturing functions, covering process volumes from approximately 1 mL to 4 L per run. The purpose is not simply to assemble a broad equipment portfolio. It is to bring production-representative conditions into design and development early enough to identify scale-dependent differences and keep transfer into routine manufacturing under control.

The Design and Development team is equipped with a range of Eppendorf refrigerated centrifuges spanning different specifications and capacity classes, including high-speed microcentrifuges for screening at approximately 1 mL scale, as well as versatile refrigerated centrifuges for routine low-speed processing, medium-volume process studies, and staged scale-up. The platform covers different processing scales, from micro-volume and high-speed applications to medium- and large-volume processing. This enables centrifugation conditions to be progressively investigated and validated as sample volumes increase, providing a continuous link between early-stage formulation screening, process development, and production-representative conditions.

Decades of Centrifugation Expertise

Eppendorf was founded in Hamburg, Germany, in 1945. In 1964, it introduced the Centrifuge 3200, the company’s first centrifuge and part of the Eppendorf Microliter System. Its centrifuge portfolio subsequently expanded from microlitre-scale sample handling to multipurpose and high-capacity applications.

The origins of the Sorvall brand can be traced to Ivan Sorvall, Inc., founded in 1930. Thermo Scientific’s current centrifugation portfolio draws on more than 75 years of centrifugation expertise, with platforms spanning laboratory research, high-speed separation and high-capacity batch processing. Thermo Fisher acquired FIBERLite Centrifuge in 2008, further integrating Fiberlite™ carbon-fiber rotor technology into its high-performance centrifugation systems. Atlas Link Technology selected these platforms not simply for their brand names, but for the engineering foundations they provide in speed control, temperature management, rotor technology and long-term operating stability. Those capabilities are then incorporated into Atlas Link Technology’s own process validation and quality management framework.

At the Center of Production: Sorvall LYNX 4000

ATLAS LINK’s manufacturing department operates multiple Thermo Scientific™ Sorvall™ LYNX 4000 floor-standing superspeed refrigerated centrifuges and maintains a substantial inventory of compatible high-performance 1 L centrifuge bottles. Multiple units support parallel conjugate processing, production continuity and equipment changeover, providing the hardware foundation for consistent execution of validated centrifugation processes.

The LYNX 4000 provides a temperature range of -10 °C to +40 °C, supports pre-cooling, and offers speed control accuracy of up to ±25 rpm. Stable refrigeration and speed control help manage the heat load generated at high speed and allow temperature-sensitive conjugates to experience more consistent force-time-temperature conditions from run to run.

Carbon-Fiber Rotors: Performance with Practical Handling

With the Fiberlite™ F10-4 × 1000 LEX carbon-fiber composite fixed-angle rotor, each LYNX 4000 run can accommodate four 1 L bottles for a total rotor capacity of 4 L. In this configuration, the maximum speed is 10,500 rpm and the maximum RCF is 20,584 × g. Across its broader compatible rotor portfolio, the LYNX 4000 platform can reach up to 24,000 rpm and 68,905 × g; these overall platform maxima do not apply to the 4 L configuration.

Fiberlite carbon-fiber composite rotors can be up to approximately 60% lighter than comparable metal rotors while providing strong corrosion and fatigue resistance. For high-capacity operations that require frequent rotor handling, the lower weight supports better day-to-day ergonomics, while the material properties are suited to repeated operation over time. The rotor family is also supported by a 15-year manufacturer’s warranty, contributing to lifecycle management.

The Auto-Lock™ rotor system enables tool-free rotor installation and exchange. Auto-ID™ automatically identifies the rotor and manages operation within its applicable parameter range, helping reduce the risks of incorrect rotor selection and overspeed settings. The value of a high-performance rotor lies not only in peak speed, but in integrating capacity, centrifugal force, temperature control and operational safety into one manageable system.

The Value of Speed and Refrigeration Is Process Stability

A high-quality centrifuge is not valuable because “faster is always better” or “colder is always better.” Its value lies in its ability to execute a validated operating window accurately and consistently. Insufficient RCF may result in incomplete particle recovery, while excessive RCF or overly long run times may lead to excessive pellet compaction, making resuspension more difficult and, in some systems, increasing the risk of particle or particle–protein complex aggregation.

Refrigerated operation must also be based on process validation. The refrigeration system helps limit temperature rise during high-speed operation and maintain suitable, repeatable conditions for temperature-sensitive conjugates. However, the set temperature is not necessarily identical to the actual sample temperature, so critical processes must still be confirmed in relation to fill volume, rotor, run time and sample characteristics.

At Atlas Link Technology, speed, refrigeration and stability are therefore treated as an integrated process capability: under defined rotor and loading conditions, every batch should experience repeatable RCF, time, temperature, and acceleration and deceleration profiles.

Risk Management: Production-Representative Equipment in Design and Development

The same rpm does not produce the same RCF in every rotor. RCF changes with rotor radius, and when a process moves from approximately 1 mL to 4 L, bottle geometry, fill volume, sedimentation path, medium viscosity, temperature, and acceleration and deceleration profiles can all affect sedimentation behaviour, pellet compaction, supernatant carryover and resuspension.

For this reason, Atlas Link Technology’s Design and Development team has established centrifugation capabilities from microscale screening, routine low-speed processing and medium-volume process studies through to production confirmation at the 4 L scale. By incorporating centrifuges, rotors, centrifuge bottles and temperature-control conditions that are the same as or representative of those used in production during the design and development stage, potential scale-up-related differences can be evaluated at an early stage, providing a basis for subsequent process validation and design transfer.

From Eppendorf high-speed refrigerated microcentrifugation, through staged scale-up using refrigerated centrifuges across multiple capacity classes, to production-representative confirmation on the Sorvall LYNX 4000, the objective is not simply to use a larger container. It is to carry one verifiable centrifugation logic from design and development into manufacturing.

Turning Equipment Capability into a Foundation for Consistent Output

Atlas Link Technology manages centrifuges, rotors and centrifuge bottles within a unified equipment and process framework covering asset identification, acceptance, operator training, calibration checks, cleaning and maintenance, rotor lifecycle management, and deviation traceability. Equipment provides controllable capability; consistent output depends on the combined effect of equipment performance, validated process parameters, standardized operation and quality management.

Multiple LYNX 4000 units and a sufficient inventory of compatible centrifuge bottles support batch processing, production continuity and batch-to-batch comparability. The complete centrifugation path available to the Design and Development team brings scale-up and transfer risks into evaluation and control at an earlier stage.From approximately 1 mL to 4 L, Atlas Link Technology’s objective is to make each centrifugation step more stable, repeatable and traceable—and to help design and development outputs move more smoothly into routine manufacturing.