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Author Notes:

Andrei G. Fedorov, agf@gatech.edu

A.G.F. and P.A.K. conceived of the idea for the microfluidic platform and formulated research goals. A.L.C. designed, built, validated, and applied the platform with assistance and supervision from M.A.C., P.A.K, and A.G.F. Cell culture, harvesting, and biological insight were provided by D.G. and A.C.B-W. A.L.C. interpreted results and wrote the initial draft with significant input from M.A.C., P.A.K, and A.G.F. The final draft was completed with assistance from all authors.

The work described herein is supported by NSF Center for Cell Manufacturing Technologies (CMaT) Award 1648035, NSF Graduate Research Fellowship Grant No. DGE-1148903, the Marcus Center for Therapeutic Cell Characterization and Manufacturing Collaboration Grant in Cell Manufacturing, the Georgia Tech Foundation, and the Georgia Research Alliance. Partial support was also provided by Grant Number R01 GM138802 from the National Institute of General Medical Science (NIGMS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NSF, NIGMS or NIH. Device fabrication was performed at the Georgia Tech Institute for Electronics and Nanotechnology, a member of the National Nanotechnology Coordinated Infrastructure (NNCI), which is supported by National Science Foundation Grant ECCS-2025462. The authors would like to acknowledge the Roy lab, specifically Nate Dwarshuis and Miguel Armenta Ochoa, and the Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M) staff for technical assistance with cell culture experiments.

Mason Chilmonczyk and Andrei Fedorov are inventors of the technology and are pursuing its commercialization. The terms of this arrangement have been reviewed and approved by Georgia Tech in accordance with its conflict of interest policies.

Subject:

Keywords:

  • mass spectrometry
  • cells

Sample-to-Analysis Platform for Rapid Intracellular Mass Spectrometry from Small Numbers of Cells

Journal Title:

LAB ON A CHIP

Volume:

Volume 21, Number 23

Publisher:

, Pages 4696-4706

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Real-time, advanced diagnostics of the biochemical state within cells remains a significant challenge for research and development, production, and application of cell-based therapies. The fundamental biochemical processes and mechanisms of action of such advanced therapies are still largely unknown, including the critical quality attributes that correlate to therapeutic function, performance, and potency and the critical process parameters that impact quality throughout cell therapy manufacturing. An integrated microfluidic platform has been developed for in-line analysis of a small number of cells via direct infusion nano-electrospray ionization mass spectrometry. Central to this platform is a microfabricated cell processing device that prepares cells from limited sample volumes removed directly from cell culture systems. The sample-to-analysis workflow overcomes the labor intensive, time-consuming, and destructive nature of existing mass spectrometry approaches for analysis of cells. By providing rapid, high-throughput analyses of the intracellular state, this platform enables untargeted discovery of critical quality attributes and their real-time, in-process monitoring.
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