Creating a low-cost cell sorter prototype

The high cost and complexity of cell and gene therapy manufacturing continue to limit patient access and pose significant challenges for companies looking to scale their technology. To address these barriers, new tools are needed to deliver faster, more efficient data on quality, safety, and efficacy during the manufacturing process.

We set out to prove that in-process, real-time analytics can be implemented both quickly and cost-effectively in cell and gene therapy process development. Using off-the-shelf components, we developed a proof of concept for a low-cost, label-free cell sorter. The prototype directly integrates measurement capabilities in-process, offering the potential for improved insights, reduced risk of batch failure, and better scalability for cell and gene therapy production.

Cell and gene therapies | Applied science | Microfluidics | Optics

The challenges of manufacturing cell and gene therapies

Cell and gene therapies are increasingly emerging as life-saving treatments for a wide range of conditions, from cancer to rare diseases. Although many have achieved regulatory approval, the industry continues to face significant commercial hurdles in scaling up production, due to high manufacturing costs and offline quality control processes that can take weeks to complete. Without technical innovation to address these challenges, the market risks slowing down—significantly limiting patient access.

A low-cost solution to early-stage measurement and process understanding

To help address this challenge, we developed a prototype for a low-cost cell sorter that enables effective quality control measurements during process development or manufacturing. The prototype integrates advanced image processing techniques for precise identification and separation of cells based on their phenotype.

Designed for label-free sorting, the device can separate spherical particles based solely on their size and shape. This eliminates the need to modify particles—or cells in a therapy process—before entering the device, helping streamline the integration of quality control and analytics by combining multiple steps into a single system.

Fast and cost-efficient prototype development

Our applied science experts rapidly developed the cell sorter rig by integrating and customizing commercial off-the-shelf components to leverage economies of scale—including a camera, optics, Raspberry Pi, and existing image processing libraries. This modular design enables seamless integration into cell therapy process development platforms, allowing for rapid data collection and fast iteration.

Integrating microfluidics and optics technology

Our team began by defining the functional and technical requirements for the prototype during an initial product definition phase. To simulate morphology-based cell sorting, we selected two types of spherical polystyrene particles, which were flowed through a microfluidic cartridge. These particles were detected and classified in real time using a custom image processing algorithm, before being actively directed into separate output channels.

We employed a systems engineering approach to integrate fluidics and optics into a compact, modular design that interfaces precisely with the microfluidic cartridge. After validating the concept with the benchtop prototype, we advanced the design by miniaturizing the system. This included custom-fabricated microfluidic chips and an optimized optical setup, resulting in a more robust and scalable solution.

Man at computer working on microfluidic CAD

Compact system development

To enable seamless integration of the sensing system in in-line, on-line, or at-line configurations, we used optical simulation software to compact and refine the design. Our applied scientists explored multiple strategies—including reduced-size optics, folding mirrors, and relay systems—to achieve a smaller footprint without compromising performance.

The simulations allowed us to evaluate key parameters such as image resolution, contrast, and aberration throughout the process. This also enabled direct comparisons between off-the-shelf components and custom lens designs, helping to balance performance with cost.

Simulations offer an effective way to accelerate development, reduce risks, and identify challenges early—ultimately saving costs in the long run. By applying optical simulation, we were able to meet both geometric and budgetary constraints while maintaining acceptable optical performance. It also provided early insights into mechanical and manufacturing considerations, including a range of tolerances, allowing us to better understand their potential impacts.
Olympia Pachoumi, Senior Applied Science Specialist, Team Consulting

A new approach to cell and gene therapy in-process analytics

By shifting analytics from offline to real-time, this approach highlights the potential for cell and gene therapy manufacturers to reduce reliance on slow and expensive quality control testing. Instead, it brings critical measurements directly into the manufacturing process.

The result is a faster, more predictable, and more robust development cycle for cell therapies—ultimately reducing or even eliminating the delays associated with traditional release testing.

Our approach illustrates how practical, data-driven solutions can empower developers to streamline manufacturing, shorten time to market, and strengthen their case for both regulatory approval and commercial success.

Ongoing advances in technology miniaturization and artificial intelligence are poised to accelerate the evolution of multimodal process analytical technologies—particularly those that are contactless and label-free. These innovations hold the potential to significantly reduce the cost and complexity of developing cell and gene therapies, while ensuring consistent product quality.
Laureline Mahe, Head of Applied Science, Team Consulting