A novel multi-frequency trans-endothelial electrical resistance (MTEER) sensor array to monitor blood-brain barrier integrity

SENSORS AND ACTUATORS B-CHEMICAL

卷:334

Article

Badiola-Mateos, Maider^1,2  Di Giuseppe, Davide^5,6  Paoli, Roberto^1,2  Lopez-Martinez, Maria Jose^1,2,3  Mencattini, Arianna^5,6  Samitier, Josep^1,2,3,4  Martinelli, Eugenio^5,6 

[1] Barcelona Inst Sci & Technol BIST, Inst Bioengn Catalonia IBEC, Nanobioengn Grp, 12 Baldiri Reixac 15-21, Barcelona 08028, Spain

[2] Univ Barcelona, Dept Elect & Biomed Engn, Marti & Franques 1, Barcelona 08028, Spain

[3] Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Monforte Lemos 3-5,Pabellon 11, Madrid 28029, Spain

[4] Univ Barcelona UB, Inst Nanosci & Nanotechnol, Barcelona 08028, Spain

[5] Univ Roma Tor Vergata, Dept Elect Engn, Via Politecn 1, I-00133 Rome, Italy

[6] Univ Roma Tor Vergata, Interdisciplinary Ctr Adv Studies Lab On Chip & O, Via Montpellier 1, I-00133 Rome, Italy

关键词: Electrical impedance spectroscopy;    Microelectrodes;    Impedance sensors;    MTEER;    Rapid prototyping;    Machine learning;    Blood-Brain barrier;    Cellular barrier integrity monitoring;   

DOI  :  10.1016/j.snb.2021.129599

来源: Elsevier

【 摘 要 】

The blood-brain barrier (BBB) is a dynamic cellular barrier that regulates brain nutrient supply, waste efflux, and paracellular diffusion through specialized junctional complexes. Finding a system to mimic and monitor BBB integrity (i.e., to be able to assess the effect of certain compounds on opening or closing the barrier) is of vital importance in several pathologies. This work aims to overcome some limitations of current barrier integrity measuring techniques thanks to a multi-layer microfluidic platform with integrated electrodes and Multi frequency Trans-Endothelial Electrical Resistance (MTEER) in synergy with machine learning algorithms. MTEER measurements are performed across the barrier in a range of frequencies up to 10 MHz highlighting the presence of information on different frequency ranges. Results show that the proposed platform can detect barrier formation, opening, and regeneration afterwards, correlating with the results obtained from immunostaining of junctional complexes. This model presents novel techniques for a future biological barrier in-vitro studies that could potentially help on elucidating barrier opening or sealing on treatments with different drugs.

【 授权许可】

Free