Citation: JIANG Ze, ZHANG Xuan, LIU Jin-Hui, WEI Xing, CHEN Ming-Li, WANG Jian-Hua. Construction of Human Blood-Brain Barrier in Vitro and Permeability Evaluation of Metal Ions or Metal Nanoparticles[J]. Chinese Journal of Analytical Chemistry, ;2021, 49(10): 1657-1665. doi: 10.19756/j.issn.0253-3820.210406 shu

Construction of Human Blood-Brain Barrier in Vitro and Permeability Evaluation of Metal Ions or Metal Nanoparticles

Department of Chemistry, College of Science, Northeastern University, Shenyang 110819, China

Corresponding author: CHEN Ming-Li, WANG Jian-Hua,
Received Date: 1 April 2021
Revised Date: 16 August 2021

Fund Project: Supported by the National Natural Science Foundation of China (Nos.21727811, 21922402), the Fundamental Research Funds for the Central Universities (Nos.N2005003, N2105017), the Liaoning Revitalization Talents Program (No.XLYC1802016) and the Innovative Talents Support Program for Universities of Liaoning Province, China (No.ZX20200088).

An in vitro blood-brain barrier (BBB) microfluidic chip was constructed to evaluate the transmittance of metal and metal nanoparticles. By combining with the "sandwich" blood-brain barrier model, the concentration gradient generation unit was integrated on the chip to realize permeability evaluation of metal-related components at different concentrations. bEnd.3 cells were employed as BBB model cells, and inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure metal ions and metal nanoparticles trans-membrane and barrier absorption in the model in vitro. The mixing effect of the fluid in the chip channel was theoretically simulated by Comsol simulation software. The actual mixing effect was evaluated with samples including cadmium and Rhodamine B solution, and the reliability of the concentration gradient generation unit of the actual sample was evaluated by atomic absorption spectroscopy. In the barrier permeability evaluation experiment, the BBB permeability of sodium fluorescein was (5.45±0.48)×10^-6 cm/s, which was basically consistent with the previous research. The chip could generate stable concentration generation, realize in vitro simulation of BBB organs and evaluation of metal permeability, which was expected to be used in the future in the central nervous system drug screening and metal, nanoparticle neurotoxicity assessment and other fields.
- Microfluidics,
- Blood-brain barrier,
- Metal toxicity,
- Inductively coupled plasma-mass spectrometry
1. [1]
  BOOTH R, KIM H. Lab Chip, 2012, 12(10):1784-1792.
2. [2]
  PARDRIDGE W M, OLDENDORF W H, CANCILLA P, FRANK H J L. Ann. Intern. Med., 1986, 105(1):82-95.
3. [3]
  FERRI C P, PRINCE M, BRAYNE C, BRODATY H, FRATIGLIONI L, GANGULI M, HALL K, HASEGAWA K, HENDRIE H, HUANG Y, JORM A, MATHERS C, MENEZES P R, RIMMER E, SCAZUFCA M. Lancet, 2005, 366(9503):2112-2117.
4. [4]
  PANGALOS M N, SCHECHTER L E, HURKO O. Drug Discov. Today, 2007, 6(10):521-532.
5. [5]
  YU L Y, LI R L, WU H L, ZHANG S F, CHAI M W, SHEN X X, HONG M, LIN H. Chin. J. Anal. Chem., 2020, 48(8):e20098-e20106.
6. [6]
  BOONSTRA E, DE KLEIJN R, COLZATO L S, ALKEMADE A, FORSTMANN B U, NIEUWENHUIS S. Front. Psychol., 2015, 6(10):1520-1525.
7. [7]
  ZHENG W, ASCHNER M, GHERSI-EGEA J F. Toxicol. Appl. Pharmacol., 2003, 192(1):1-11.
8. [8]
  GRIEP L M, WOLBERS F, DE WAGENAAR B, TER BRAAK P M, WEKSLER B B, ROMERO I A, COURAUD P O, VERMES I, MEER A D, BERG A. BIOMED. Microdevices, 2013, 15(1):145-150.
9. [9]
  WALTER F R, VALKAI S, KINCSES A, PETNEHÁZI A, CZELLER T, VESZELKA S, ORMOS P, DELI M A, DER A. Sens. Actuators, B, 2016, 222(1):1209-1219.
10. [10]
  SHIN Y, HAN S, JEON J S, YAMAMOTO K, CHUNG S. Nat. Protoc., 2012, 7(7):1247-1259.
11. [11]
  SUNG K E, GUI S, PEHLKE C, TRIER S M, ELICEIRI K W, KEELY P J, FRIEDL A, BEEBE D J. Biomaterials, 2009, 30(27):4833-4841.
12. [12]
  BROWN J A, PENSABENE V, MARKOV D A, ALLWARDT V, NEELY M D, SHI M, BRITT C M, HOILETT O S, YANG Q, BREWER B M. Biomicrofluidics, 2015, 9(5):054124.
13. [13]
  GRIEP L M, WOLBERS F, DE WAGENAAR B, TER BRAAK P M, WEKSLER B B, ROMERO I A, COURAUD P O, VERMES I, VAN DER MEER A D, VAN DER BERG A. Biomed. Microdevices, 2013, 15(1):145-150.
14. [14]
  ODDO A, PENG B, TONG Z, WEI Y, TONG W Y, THISSEN H, VOELCKER N H. Trends Biotechnol., 2019; 37(12):1295-1314.
15. [15]
  WEVERS N R, VAN VUGHT R, WILSCHUT K J, NICOLAS A, CHIANG C, LANZ H L, TRIETSCH S J, JOORE J, VULTO P. Sci. Rep., 2016, 6(12):38856.
16. [16]
  ADRIANI G, MA D, PAVESI A, KAMM R D, GOH E L K. Lab Chip, 2017, 17(3):448-459.
17. [17]
  PRABHAKARPANDIAN B, SHEN M C, NICHOLS J B, MILLS I R, SIDORYK-WEGRZYNOWICZ M, ASCHNER M, PANT K. Lab Chip, 2013, 13(6):1093-1101.
18. [18]
  MAX I B, PETER C S. Integr. Biol., 2016, 8(9):976-984.
19. [19]
  WOLFF A, ANTFOLK M, BRODIN B, TENJE M. J. Pharm. Sci., 2015, 104(9):2727-2746.
20. [20]
  HUANG Q S, MAO S F, KHAN M Z, LIN J M. Chem. Commun., 2018, 54(21):2595-2598.
21. [21]
  ZHANG X, WEI X, MEN X, JIANG Z, YE W Q, CHEN M L, YANG T, XU Z R, WANG J H. Anal. Chem., 2020, 92(9):6604-6612.
22. [22]
  MAO S F, ZHANG W L, HUANG Q S, KHAN M, LI H F, KATSUMI U, LIN J M. Angew. Chem., Int. Ed,, 2017, 57(1):236-240.
23. [23]
  TOMITA S, SAKAO M, KURITA R, NIWA O, YOSHIMOTO K. Chem. Sci., 2015, 6(10):5831-5836.
24. [24]
  WEI X, ZHANG X, GUO R, CHEN M L, YANG T, XU Z R, WANG J H. Anal. Chem., 2019, 91(24):15826-15832.
25. [25]
  SHEN S F, ZHANG X, ZHANG F J, WANG D F, LONG D D, NIU Y B. Talanta, 2020, 208(2):120477.
26. [26]
  FENG D S, XU T R, LI H, SHI X Z, XU G W. J. Anal. Test., 2020, 4:198-209.
27. [27]
  SHAO X J, GAO D, CHEN Y L, JIN F, HU G N, JIANG Y Y, LIU H X. Anal. Chim. Acta, 2016, 934(8):186-193.
28. [28]
  WANG J D, KHAFAGY E, KHANAFER K, TAKAYAMA S, ELSAYED M E H. Mol. Pharm., 2016, 13(3):895-906.
29. [29]
  TOBWALA S, WANG H J, CAREY J, BANKS W, ERCAL N. Toxics, 2014, 2(2):258-275.
30. [30]
  ZHOU Y, PENG Z, SEVEN E S, LEBLANC R M. J. Controlled Release, 2018, 270(1):290-303.
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