A Multifunctional Microfluidic Device for Tailoring Analytical Assay Development for Multiproduct Cell Therapy Products (CTPs)

Abstract

Background & Aim

The rising demand for cell therapies necessitates innovative tools to streamline analytical development & QC assays. We propose a microfluidic device to transform analytical workflows by handling small samples, reducing reagents, & automating processes.

Methodology

This device minimizes reagent requirements while maintaining high throughput, enabling cost-efficient and scalable processes. Its microfluidic architecture precisely manipulates & separates T cells from whole blood samples, reducing sample volume significantly compared to conventional methods. Beyond T cell isolation, the device integrates a multifunctional platform capable of performing analytical assays, including ELISA, effectively replacing traditional 96-well plates. This integration enhances its utility by enabling real-time cytokine profiling, immunophenotyping, high-sensitivity biomarker detection, single-cell analysis & multiplexed assays on a single platform.

Results

The design of this microfluidic device was developed after thorough review of existing literature & iterative modifications. Key considerations included device dimensions, operational sequences, particle size compatibility, reagent material compatibility, hydrophobicity, and detection sensitivity. The final configuration comprises two pairs of hexagonal channels connected via one inlet and two outlets, utilizing a herringbone structure to optimize cell capture & retention. This structure disrupts flow, increasing turbulence & enhancing cell interaction with channel surfaces. The device leverages microfluidic principles, manipulating fluid behavior using microliter to picoliter volumes with channel dimensions in the micrometer range. It adheres to the Hele-Shaw flow property, defined as Stokes Flow between two parallel plates separated by a narrow gap, ensuring laminar flows with low Reynolds numbers. Fabricated from advanced polymers like PDMS and PMMA, the device ensures durability, biocompatibility, and seamless integration with automated workflows. It supports parallel processing of multiple samples, reducing assay time while maintaining precision and reproducibility. The system is compatible with existing laboratory tools like flow cytometry & imaging systems, enabling effortless adoption in clinical and industrial settings.

Conclusion

By combining versatility, scalability, and cost-efficiency, this microfluidic system represents a robust platform for CAR T analytical development, poised to advance the manufacturing and QC landscapes of CGT.