TY - CHAP

T1 - Microfluidic Devices as Process Development Tools for Cellular Therapy Manufacturing

AU - Aranda Hernandez, Jorge

AU - Heuer, Christopher

AU - Bahnemann, Janina

AU - Szita, Nicolas

N1 - Funding Information: We would like to acknowledge the excellent service of the Servier Medical Art (SMART) website https://smart.servier.com/ providing icons and cartoons free-of-charge that we used for our illustrations, including the graphical abstract. UCL Biochemical Engineering hosts the Future Targeted Healthcare Manufacturing Hub in collaboration with UK universities and with funding from the UK Engineering & Physical Sciences Research Council (EPSRC, EP/P006485/1) and a consortium of industrial users and sector organisations. The authors also gratefully acknowledge the Engineering and Physical Sciences Research Council (EPSRC, EP/I005471/1, EP/ L01520X/1, EP/S01778X/1, EP/S021868/1) and the Biotechnology and Biological Sciences Research Council (BBSRC, BB/L000997/1) for further funding.

PY - 2022

Y1 - 2022

N2 - Cellular therapies are creating a paradigm shift in the biomanufacturing industry. Particularly for autologous therapies, small-scale processing methods are better suited than the large-scale approaches that are traditionally employed in the industry. Current small-scale methods for manufacturing personalized cell therapies, however, are labour-intensive and involve a number of 'open events'. To overcome these challenges, new cell manufacturing platforms following a GMP-in-a-box concept have recently come on the market (GMP: Good Manufacturing Practice). These are closed automated systems with built-in pumps for fluid handling and sensors for in-process monitoring. At a much smaller scale, microfluidic devices exhibit many of the same features as current GMP-in-a-box systems. They are closed systems, fluids can be processed and manipulated, and sensors integrated for real-time detection of process variables. Fabricated from polymers, they can be made disposable, i.e. single-use. Furthermore, microfluidics offers exquisite spatiotemporal control over the cellular microenvironment, promising both reproducibility and control of outcomes. In this chapter, we consider the challenges in cell manufacturing, highlight recent advances of microfluidic devices for each of the main process steps, and summarize our findings on the current state of the art. As microfluidic cell culture devices have been reported for both adherent and suspension cell cultures, we report on devices for the key process steps, or unit operations, of both stem cell therapies and cell-based immunotherapies.

AB - Cellular therapies are creating a paradigm shift in the biomanufacturing industry. Particularly for autologous therapies, small-scale processing methods are better suited than the large-scale approaches that are traditionally employed in the industry. Current small-scale methods for manufacturing personalized cell therapies, however, are labour-intensive and involve a number of 'open events'. To overcome these challenges, new cell manufacturing platforms following a GMP-in-a-box concept have recently come on the market (GMP: Good Manufacturing Practice). These are closed automated systems with built-in pumps for fluid handling and sensors for in-process monitoring. At a much smaller scale, microfluidic devices exhibit many of the same features as current GMP-in-a-box systems. They are closed systems, fluids can be processed and manipulated, and sensors integrated for real-time detection of process variables. Fabricated from polymers, they can be made disposable, i.e. single-use. Furthermore, microfluidics offers exquisite spatiotemporal control over the cellular microenvironment, promising both reproducibility and control of outcomes. In this chapter, we consider the challenges in cell manufacturing, highlight recent advances of microfluidic devices for each of the main process steps, and summarize our findings on the current state of the art. As microfluidic cell culture devices have been reported for both adherent and suspension cell cultures, we report on devices for the key process steps, or unit operations, of both stem cell therapies and cell-based immunotherapies.

KW - Biomanufacturing

KW - CAR-T

KW - Cell and gene therapy

KW - Cell culture

KW - Cell manufacturing

KW - GMP-in-a-box

KW - Immunotherapy

KW - Medical biotechnology

KW - Microfluidics

KW - Scale-down

KW - Scale-up

KW - Stem cells

KW - Translation

UR - http://www.scopus.com/inward/record.url?scp=85135379046&partnerID=8YFLogxK

U2 - 10.1007/10_2021_169

DO - 10.1007/10_2021_169

M3 - Contribution to book/anthology

C2 - 34410457

SN - 978-3-031-04187-7

T3 - Advances in Biochemical Engineering/Biotechnology

SP - 101

EP - 127

BT - Microfluidics in Biotechnology

CY - Cham

ER -