Microphysiological system with continuous analysis of albumin for hepatotoxicity modeling and drug screening

Arun Asif; Sung Hyuk Park; Afaque Manzoor Soomro; Muhammad Asad Ullah Khalid; Abdul Rahim Chattikatikatuveli Salih; Bohye Kang; Faheem Ahmed; Kyung Hwan Kim; Kyung Hyun Choi

Journal of Industrial and Engineering Chemistry, Vol.98, 318-326, June, 2021

DOI10.1016/j.jiec.2021.03.035 Export Citation

Microphysiological system with continuous analysis of albumin for hepatotoxicity modeling and drug screening

Arun Asif¹, Sung Hyuk Park¹, Afaque Manzoor Soomro^{1, 2}, Muhammad Asad Ullah Khalid¹, Abdul Rahim Chattikatikatuveli Salih¹, Bohye Kang¹, Faheem Ahmed¹, Kyung Hwan Kim¹, and Kyung Hyun Choi^{1, 3, †}

¹Advanced Micro Mechatronics Lab, Department of Mechatronics Engineering, Jeju National University, Jeju-si, Jeju-do, 63243, Republic of Korea
²Department of Electrical Engineering, Sukkur IBA University, Airport Road, Sukkur, Sindh, 56200, Pakistan
³BioSpero, Inc., Jeju–do, Republic of Korea

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In microfluidics, the emerging field of microphysiological systems (MPS) is overcoming the challenge of physiological irrelevancy by animal models for drug discovery and development. Liver function is critically influenced by drugs owing to its role in drug metabolism and detoxification. Human serum albumin (HSA) is one of the most important secreted biomarkers which indicate normal liver function. A microfluidic albumin immunosensor was developed to be integrated with liver-on-a-chip MPS for continuous feedback over disease modeling and treatment. A gold-electrode based electrochemical immunosensor was established by anti-HSA antibody immobilization. The liver MPS was found to be efficient for live monitoring of disease modelling and drug treatment over the period of 6 days. The system emulated and analyzed real-time toxicity modeling with HSA sensing. The detection limit of integrated sensor was 1 mg/ml with successive reproducibility. The proposed sensor was also validated with metabolic biomarkers’ assays. Molecular assays supported the sensor monitoring and depicted liver injury and recovery. The liver MPS with combined albumin sensor chip may be a promising platform to mimic real-time drug assessment.

Keywords:Albumin;Immunosensor;Microphysiological system;Microfluidic;Impedance

[References]

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[1] Rodrigues RO, Sousa PC, Gaspar J, Banobre-Lopez M, Lima R, Minas G, Small, 16, 200351 (2020)

[2] Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, et al., PNAS, 110, 3507 (2013)

[3] Curry SH, Ann. N. Y. Acad. Sci., 993(5), 69 (2003)

[4] Zhao Y, Kankala RK, Wang SB, Chen AZ, Molecules, 24, 675 (2019)

[5] Soucy JR, Bindas AJ, Koppes AN, Koppes RAJI, iScience, 21, 521 (2019)

[6] Nguyen P, Leray V, Diez M, Serisier S, Bloc’h JL, Siliart B, Dumon H, J. Anim. Physiol. Anim. Nutr., 92, 272 (2008)

[7] Dehne EM, Hasenberg T, Marx U, Future Science, OA3, FSO018 (2017)

[8] Giordano L, Mihaila SM, Amirabadi HE, Masereeuw R, Trends Biotechnol (in press) (2021).

[9] Trapecar M, Wogram E, Svoboda D, Communal C, Omer A, Lungjangwa T, Sphabmixay P, Velazquez J, Schneider K, Wright C, Sci. Adv., 7, eabd17 (2021)

[10] Feldmann G, Penaud-Laurencin J, Crassous J, Benhamou J, Gastroenterol., 63, 1036 (1972)

[11] Greenblatt D, Koch-Weser J, Eur. J. Clin. Pharmacol., 7, 259 (1974)

[12] Rebelo R, Barbosa AI, Caballero D, Kwon IK, Oliveira JM, Kundu SC, Reis RL, Correlo V, Bioelectronics, 130, 20 (2019)

[13] Meghani N, Kim KH, Kim SH, Lee SH, Choi KH, Arch. Pharm. Res., 43, 503 (2020)

[14] Riahi R, Shaegh SA, Ghaderi M, Zhang YS, Shin SR, Aleman J, Massa S, Kim D, Dokmeci MR, Khademhosseini A, Sci. Rep., 6, 1 (2016)

[15] Zhang X, Chen G, Bian F, Cai L, Zhao Y, Adv. Mater., 37(31), 190282 (2019)

[16] Zhang YS, Aleman J, Shin SR, Kilic T, Kim D, Shaegh SA, Massa S, Riahi R, Chae S, Hu N, PNAS, 114(12), E2293 (2017)

[17] Ehrlich A, Duche D, Ouedraogo G, Nahmias Y, Annu. Rev. Biomed. Eng, 21, 219 (2019)

[18] Zhou Q, Patel D, Kwa T, Haque A, Matharu Z, Stybayeva G, Gao Y, Diehl AM, Revzin A, Lab Chip, 15, 4467 (2015)

[19] Theobald J, Ghanem A, Wallisch P, Banaeiyan AA, Andrade-Navarro MA, Taskova K, Haltmeier M, Kurtz A, Becker H, Reuter S, ACS Biomater. Sci. Eng., 4, 78 (2018)

[20] Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarro LM, Bradshaw CR, Allen GE, Arnes-Benito R, Sidorova O, Gaspersz M, Nat. Med., 23, 1424 (2017)

[21] Lancaster MA, Knoblich JA, Science, 345 (2014)

[22] Lee H, Chae S, Kim JY, Han W, Kim J, Choi Y, Cho DW, Biofabrication, 11, 025001 (2019)

[23] Kim Y, Kang K, Jeong J, Paik SS, Kim JS, Park SA, Kim WD, Park J, Choi D, Ann. Surg. TreatRes., 92, 67 (2017)

[24] Li L, Gokduman K, Gokaltun A, Yarmush ML, Usta O, Nanomed., 17, 2209 (2019)

[25] Esch MB, Ueno H, Applegate DR, Shuler ML, Lab Chip, 16, 2719 (2016)

[26] Gori M, Simonelli MC, Giannitelli SM, Businaro L, Trombetta M, Rainer A, PLoS One, 11, e01597 (2016)

[27] Kang T, Park C, Meghani N, Tran TT, Tran PH, Lee BJ, Pharmaceutics, 12, 555 (2020)

[28] Yang F, Bian CB, Zhu LL, Zhao GX, Huang ZX, Huang MD, J. Struct. Biol., 157(2), 348 (2007)

[29] Levitt DG, Levitt MD, Int.J. Gen. Med., 9, 229 (2016)

[30] David SA, Endotoxins in health and disease, Marcel Dekker, New York, pp.413 1999.

[31] Bertucci C, Domenici E, Curr. Med. Chem., 9, 1463 (2002)

[32] Zheng CM, Wu CC, Lu CL, Hou YC, Wu MS, Hsu YH, Chen R, Chang TJ, Shyu JF, Lin YF, Lu KC, Int. J. Med. Sci., 16, 1583 (2019)

[33] Rena G, Hardie DG, Pearson ER, Diabetologia, 60, 1577 (2017)

[34] Matafome P, Louro T, Rodrigues L, Crisostomo J, Nunes E, Amaral C, Monteiro P, Cipriano A, Seica R, Diabetes Metab. Res. Rev., 27, 54 (2011)

[35] Asif A, Kim KF, Jabbar F, Kim S, Choi KH, Microfluid Nanofluidics., 24 (2020)

[36] Salih ARC, Farooqi HMU, Kim YS, Lee SH, Choi KH, Microelectron. Eng., 232, 111405 (2020)

[37] Barbier L, Ferhat M, Salame E, Robin A, Herbelin A, Gombert JM, Silvain C, Barbarin A, Front Immunol., 10, 2014 (2019)

[38] Alegre F, Pelegrin P, Feldstein AE, Seminars in liver disease, 37, Thieme Medical Publishers, pp. 119 May (02) 2017.