Swedish researchers have developed a microfluidic chip that they hope will allow for easier monitoring of monoclonal antibody (mAb) production. The protein cartridge, developed by a team from KTH Royal Institute of Technology in Stockholm, allows for the simultaneous analysis of up to four different proteins in the cell culture in a bioreactor.
The technology aims to help manufacturers monitor the concentration of undesirable proteins produced by cells, so-called host cell proteins (HCPs), as well as the product, automatically and in real time.
“Most of these measurements are currently done offline by taking samples from the bioreactor at various points,” explains Inês F. Pinto, PhD, a postdoctoral researcher in the division of nanobiotechnology. Today this takes time and resources and can be limited in small screening bioreactors because you have to collect high volumes of samples, so it limits how many analyses can be done.”
Designed for an automated workflow
The protein chip is designed to fit into an automated workflow, whereby a volume of liquid is collected by an autosampler, removing the cells, and then processed within a specialized liquid handler.
According to Pinto, the idea is for dilution to be completed by a pipetting robot, before the sample is flowed through the chip, where proteins are detected automatically.
The chip is currently a prototype, and the sample is still being manually collected. “One of the things still missing is to have everything combined and integrated into a single standalone instrument,” she says.
The prototype can detect multiple proteins at once, including HCPs produced by Chinese Hamster Ovary (CHO) cells. HCPs can cause immune reactions in patients. The chip also can detect elevated levels of high mannose on mAbs in culture without purification. This glycan clears therapies faster from the body making them less effective. Fucose on mAbs, which is important for therapeutic pathways involving immune function, could be detected as well.
Pinto says the prototype performs as well at HCP detection as standard well-plate ELISA kits. It has also detected high-mannose antibodies with a similar sensitivity to HPLC-MS—a gold-standard technique.
The team now hopes to raise more funding to continue their research, with the hope of developing an integrated instrument within the next few years.
The protein chip was developed as part of the EU-funded iConsensus consortium, coordinated by associate professor Veronique Chotteau, PhD, at KTH and which included Sanofi, Pfizer, GSK and Bayer, and other pharmaceutical companies, and finished last year.