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

被引:16
作者
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 ]
机构
[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;
D O I
10.1016/j.snb.2021.129599
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
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.
引用
收藏
页数:10
相关论文
共 42 条
[1]   Blood-brain barrier structure and function and the challenges for CNS drug delivery [J].
Abbott, N. Joan .
JOURNAL OF INHERITED METABOLIC DISEASE, 2013, 36 (03) :437-449
[2]   Structure and function of the blood-brain barrier [J].
Abbott, N. Joan ;
Patabendige, Adjanie A. K. ;
Dolman, Diana E. M. ;
Yusof, Siti R. ;
Begley, David J. .
NEUROBIOLOGY OF DISEASE, 2010, 37 (01) :13-25
[3]  
[Anonymous], 2009, IMPEDANCE MEASUREMEN, P140
[4]   Pericytes regulate the blood-brain barrier [J].
Armulik, Annika ;
Genove, Guillem ;
Mae, Maarja ;
Nisancioglu, Maya H. ;
Wallgard, Elisabet ;
Niaudet, Colin ;
He, Liqun ;
Norlin, Jenny ;
Lindblom, Per ;
Strittmatter, Karin ;
Johansson, Bengt R. ;
Betsholtz, Christer .
NATURE, 2010, 468 (7323) :557-U231
[5]   Classification tools in chemistry. Part 1: linear models. PLS-DA [J].
Ballabio, Davide ;
Consonni, Viviana .
ANALYTICAL METHODS, 2013, 5 (16) :3790-3798
[6]   Impedance-based cell monitoring: Barrier properties and beyond [J].
Benson K. ;
Cramer S. ;
Galla H.-J. .
Fluids and Barriers of the CNS, 10 (1)
[7]   BLOOD-BRAIN BARRIER (BBB) DISRUPTION USING A DIAGNOSTIC ULTRASOUND SCANNER AND DEFINITY® IN MICE [J].
Bing, Kristin Frinkley ;
Howles, Gabriel P. ;
Qi, Yi ;
Palmeri, Mark L. ;
Nightingale, Kathryn R. .
ULTRASOUND IN MEDICINE AND BIOLOGY, 2009, 35 (08) :1298-1308
[8]   Formation and maintenance of the BBB [J].
Blanchette, Marie ;
Daneman, Richard .
MECHANISMS OF DEVELOPMENT, 2015, 138 :8-16
[9]   Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB) [J].
Booth, Ross ;
Kim, Hanseup .
LAB ON A CHIP, 2012, 12 (10) :1784-1792
[10]   A Stable and Reproducible Human Blood-Brain Barrier Model Derived from Hematopoietic Stem Cells [J].
Cecchelli, Romeo ;
Aday, Sezin ;
Sevin, Emmanuel ;
Almeida, Catarina ;
Culot, Maxime ;
Dehouck, Lucie ;
Coisne, Caroline ;
Engelhardt, Britta ;
Dehouck, Marie-Pierre ;
Ferreira, Lino .
PLOS ONE, 2014, 9 (06)