Design and Simulation of a Microfluidic System for Hydrodynamic Irrigation of In Vitro Pancreatic Islets

Abstract:

Microfluidic systems are transforming chemical and biological research by enabling precise control and analysis of fluids on a microscale. This study presents the design and computational simulation of a microfluidic system for the in vitro maintenance of pancreatic islets, critical endocrine structures of the pancreas involved in glucose regulation. Three chamber geometries-ellipsoidal, hexagonal, and rectangular-were proposed, each combined with three irrigation patterns: periphery-to-center, pole-to-pole, and a hybrid model. A total of 18 design configurations were analyzed. The irrigation channels, with a diameter of 30 µm and a bifurcation angle of 43°, were designed to mimic physiological conditions, facilitating efficient nutrient exchange. Computational fluid dynamics (CFD) simulations using ANSYS Fluent demonstrated that most designs achieved a flow rate of 14.56 nL/s, closely matching theoretical values and meeting the physiological requirements of islets. Among the proposed models, the hexagonal chamber with peripheral irrigation (single-cell configuration) and the ellipsoidal chamber with periphery-to-center irrigation (dual-cell configuration) showed optimal performance, with stable laminar flow and minimal pressure drop. These results highlight the potential of this microfluidic system as an innovative tool for diabetes research, enabling the study of islet biology, drug testing, and disease modeling under controlled conditions. Future work will focus on experimental validation and optimization of the proposed designs.

• Periodical: Journal of Biomimetics, Biomaterials and Biomedical Engineering (Volume 69)
• Pages: 93-104
• DOI: https://doi.org/10.4028/p-cdbHT7
• Online since: October 2025
• Authors: Esmeralda Zuñiga-Aguilar, Odin Ramírez-Fernández*, Omar Anaya-Reza
• Keywords: Computational Simulation, Diabetes Mellitus, Langerhans Islets, Microfluidic Models, Organ-on-a-Chip

References

[1] P. Sokolowska, E. Jastrzebska, A. Dobrzyn, Z. Brzozka, Investigation of the therapeutic potential of new antidiabetic compounds using islet-on-a-chip microfluidic model, Biosensors vol. 12 (5) (May 2022) Art. no. 5.

DOI: 10.3390/bios12050302

[2] Ozougwu JC, Obimba KC, Belonwu C, Unakalamba CB: The Pathogenesis and Pathophysiology of Type 1 and Type 2 Diabetes Mellitus. J Physiol Pathophysiol. 2013;4(4):46–57.

DOI: 10.5897/jpap2013.0001

[3] A.P. Dufresne, T.V. Ball, N.J. Balmforth, Viscoplastic Saffman–Taylor fingers with and without wall slip, J. Non-Newton. Fluid Mech. vol. 312 (Feb. 2023) 104970.

DOI: 10.1016/j.jnnfm.2022.104970

[4] American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36(Suppl 1):S67–S74.

DOI: 10.2337/dc13-s067

[5] Bauer S: Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model. Scientific Reports. 2017;7(1):1–11.

DOI: 10.1038/s41598-017-14815-w

[6] Landman GW, Bilo HJ, Houweling ST, Kleefstra N: Chromium does not belong in the diabetes treatment arsenal: current evidence and future perspectives. World J Diabetes. 2014; 5(2): 160–4.

DOI: 10.4239/wjd.v5.i2.160

[7] J. Konopka, D. Kołodziejek, M. Flont, A. ˙ Zuchowska, E. Jastrzębska, Z. Brz´ ozka, Exploring endothelial expansion on a chip, Sens. (Basel) vol. 22 (23) (Dec. 2022) 9414

DOI: 10.3390/s22239414

[8] Wendt A, Eliasson L: Pancreatic α-cells –The unsung heroes in islet function. Seminars in Cell and Developmental Biology. 2020;103:41–50.

DOI: 10.1016/j.semcdb.2020.01.006

[9] Bosco D, Armanet M, Morel P, Niclauss N, Sgroi A, Muller Y, et al.: Unique arrangement of α- and β-cells in human islets of Langerhans. Diabetes. 2010;59(5):1202–1210.

DOI: 10.2337/db09-1177

[10] Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A: The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc. Natl. Acad. Sci. U.S.A. 2006;103(7):2334–2339.

DOI: 10.1073/pnas.0510790103

[11] T. Qin, A.M. Smink, P. de Vos, Enhancing longevity of immunoisolated pancreatic islet grafts by modifying both the intracapsular and extracapsular environment, Acta Biomater. vol. 167 (Sep. 2023) 38–53.

DOI: 10.1016/j.actbio.2023.06.038

[12] J. Chmielowiec, et al., Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling, , Art. no. 1, Nat. Commun. vol. 13 (1) (Apr. 2022).

DOI: 10.1038/s41467-022-29646-1

[13] A.P. Dufresne, T.V. Ball, N.J. Balmforth, Viscoplastic Saffman–Taylor fingers with and without wall slip, J. Non-Newton. Fluid Mech. vol. 312 (Feb. 2023) 104970.

DOI: 10.1016/j.jnnfm.2022.104970

[14] F. S. A, et al., Engineering vascularized islet macroencapsulation devices: an in vitro platform to study oxygen transport in perfused immobilized pancreatic beta cell cultures, Front. Bioeng. Biotechnol. vol. 10 (2022).

DOI: 10.3389/fbioe.2022.884071

[15] D. J. McIver et al., Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements, J. Nutr., vol. 145, no. 12, p.2675–82, Dec. 2015.

DOI: 10.3945/jn.115.214569

[16] N. I. Desouki et al., Improvement in beta-islets of Langerhans in alloxan-induced diabetic rats by erythropoietin and spirulina," J. Basic Appl. Zool., vol. 71, p.20–31, Apr. 2015.

DOI: 10.1016/j.jobaz.2015.04.003

[17] P. Sokolowska, J. Janikiewicz, E. Jastrzebska, Z. Brzozka, and A. Dobrzyn, Combinations of regenerative medicine and Lab-on-a-chip systems: New hope to restoring the proper function of pancreatic islets in diabetes, Biosens. Bioelectron., vol. 167, p.112451, May 2020.

DOI: 10.1016/j.bios.2020.112451

[18] A. Essaouiba, T. Okitsu, R. Kinoshita, R. Jellali, M. Shinohara, M. Danoy, et al., "Development of a pancreas-liver organ-on-chip coculture model for organ-to-organ interaction studies," Biochem. Eng. J., vol. 164, p.107783, November 2020.

DOI: 10.1016/j.bej.2020.107783

[19] S. Malkani and S. Ayyoub, Diabetes mellitus tipo 2 | Enfermedades y condiciones | 5MinutoConsultar, Diabetes mellitus tipo 2, 2021.

[20] C. Ma, Y. Peng, H. Li, and W. Chen, Organ-on-a-Chip: A New Paradigm for Drug Development, Trends Pharmacol. Sci., vol. 42, no. 2, p.119–133, February 2021.

[21] P. Sokolowska, K. Zukowski, J. Janikiewicz, E. Jastrzebska, A. Dobrzyn, Z. Brzozka, Islet-on-a-chip: biomimetic micropillar-based microfluidic system for three dimensional pancreatic islet cell culture, Biosens. Bioelectron. vol. 183 (Jul. 2021) 113215.

DOI: 10.1016/j.bios.2021.113215

[22] Q. Wu, J. Liu, X. Wang, L. Feng, J. Wu, X. Zhu, W. Wen, and X. Gong, Organ-on-a-chip: Recent breakthroughs and future prospects, BioMed Eng. Online, 19, no. 1, p.1–19, January 2020.

DOI: 10.1186/s12938-020-0752-0

[23] J. E. Sosa-Hernández, A. M. Villalba-Rodríguez, K. D. Romero-Castillo, M. A. Aguilar-Aguila-Isaías, I. E. García-Reyes, A. Hernández-Antonio, I. Ahmed, A. Sharma, R. Parra-Saldívar, and H. M. N. Iqbal, Organs-on-a-chip module: A review from the development and applications perspective, Micromachines, vol. 9, no. 10, p.100536.

DOI: 10.3390/mi9100536

[24] Wyss Institute, "Pulmón en un chip," Wyss Institute, 2011. [Online].

[25] G.W. Landman, H.J. Bilo, S.T. Houweling, and N. Kleefstra, Chromium does not belong in the diabetes treatment arsenal: current evidence and future perspectives, World J Diabetes, vol. 5, no. 2, p.160–164, February 2014.

DOI: 10.4239/wjd.v5.i2.160

[26] World Precision Instruments, Mini peristaltic pump," WPI. [Online]. Available: https://www.wpiinc.com/var-3125-mini-peristaltic-pump.

[27] W.E. Svendsen, Chapter 2: Basic Microfluidics Theory, in J. Castillo-León and W.E. Svendsen, Eds., Lab-on-a-Chip Devices and Micro-Total Analysis Systems A practical guide, London: Springer, 2015, pp.17-26.

DOI: 10.1007/978-3-319-08687-3_2

[28] K.H. Oh, K. Lee, B. Ahn, and E.P. Furlani, "Design of pressure-driven microfluidic networks using electric circuit analogy," Lab Chip, vol. 12, no. 3, p.515–545, March 2012.

DOI: 10.1039/C2LC20799K

[29] O. Ramirez-Fernandez, F. Equihua-Guillen, A. Garcia-Lara, and E. Zuñiga-Aguilar, Design and Characterization of a Microfluidic Biological System for Bone Tissue, in Congreso Nacional de Ingeniería Biomédica, Cham, Switzerland: Springer Nature, Oct. 2023, pp.93-99.

DOI: 10.1007/978-3-031-46933-6_10

[30] L. Jasson and P.O. Carlsson, Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans, Compr. Physiol., vol. 9, no. 2, p.799–837.

DOI: 10.1002/cphy.c160050