TY - JOUR

T1 - Lab-on-a-chip for cell perturbation, lysis, and efficient separation of sub-cellular components in a continuous flow mode

AU - Rajabi, Negar

AU - Bahnemann, Janina

AU - Tzeng, Tzu Nen

AU - Platas Barradas, Oscar

AU - Zeng, An Ping

AU - Müller, Jörg

N1 - Funding information: The authors would like to thank Grischa Fuge, Uwe Jandt, Sabrina Kayo, and Simon Kern for their support in the bio-lab. The authors also gratefully acknowledge Thomas Noll from the Institute of Cell Culture Technology (University Bielefeld, Germany) for kindly supplying the CHO-K1 cells for cultivation and experiments. This research project (SysCompart, project ID 031555D) is funded by the German Federal Ministry of Research and Education (BMBF) .

PY - 2014/1/3

Y1 - 2014/1/3

N2 - A novel lab-on-a-chip is presented for the high-throughput preparation of mammalian cell samples for metabolic studies associated with cell compartmentation. The chip is directly connected to an overpressurized bioreactor, for a continuous harvest and manipulation of cells during the cultivation process. The proposed on-chip preparation technique allows the rapid cell permeabilization and separation of sub-cellular components as cytoplasm and mitochondria, both primarily responsible for cell metabolism. The microfluidic chip comprises two temperature zones (37 °C to ensure physiological conditions and 4 °C for cell quenching), which are thermally decoupled. Cells are manipulated in a continuous flow process in five connected functional modules. The key modules of the integrated chip are a rapid split-and-recombine micromixer for biological system perturbation and chemical lysis, a chaotic advection "stirred" incubation channel for reduced residence time distribution, and a spiral channel for efficient particle separation and media exchange. The bioreactor-chip system was characterized with Chinese hamster ovary cells. It exhibits a high efficiency in the lysis process and separation of sub-cellular components.

AB - A novel lab-on-a-chip is presented for the high-throughput preparation of mammalian cell samples for metabolic studies associated with cell compartmentation. The chip is directly connected to an overpressurized bioreactor, for a continuous harvest and manipulation of cells during the cultivation process. The proposed on-chip preparation technique allows the rapid cell permeabilization and separation of sub-cellular components as cytoplasm and mitochondria, both primarily responsible for cell metabolism. The microfluidic chip comprises two temperature zones (37 °C to ensure physiological conditions and 4 °C for cell quenching), which are thermally decoupled. Cells are manipulated in a continuous flow process in five connected functional modules. The key modules of the integrated chip are a rapid split-and-recombine micromixer for biological system perturbation and chemical lysis, a chaotic advection "stirred" incubation channel for reduced residence time distribution, and a spiral channel for efficient particle separation and media exchange. The bioreactor-chip system was characterized with Chinese hamster ovary cells. It exhibits a high efficiency in the lysis process and separation of sub-cellular components.

KW - Lab-on-a-chip

KW - Mammalian cell preparation

KW - Metabolomics

KW - Organelle separation

KW - Thermal decoupling

UR - http://www.scopus.com/inward/record.url?scp=84903278233&partnerID=8YFLogxK

U2 - 10.1016/j.sna.2013.12.019

DO - 10.1016/j.sna.2013.12.019

M3 - Article

AN - SCOPUS:84903278233

VL - 215

SP - 136

EP - 143

JO - Sensors and Actuators, A: Physical

JF - Sensors and Actuators, A: Physical

SN - 0924-4247

ER -