Metal-organic frameworks as an active substrate for cell-interaction studies and cell-on-a-chip platforms

Biosensors and Bioelectronics X, vol. 19, pp. 100487

Abstract

Metal-organic frameworks (MOFs) are an emerging class of materials with immense biomedical potential for their unique interactions with biological and organic materials. In this work, we select two candidate two-dimensional (2D) MOF systems based on Fe3+ and Ni2+ metal centers and 2-aminoterephthalate acid ligand (Fe-MOF and Ni-MOF) and evaluate their performance as an active interface for study of cell-interactions. 2D Fe-MOF and Ni-MOF were synthesized onto hydroxyl-modified gold and glass substrates using a layer-by-layer liquid-phase-epitaxy (LbL-LPE) growth at room temperature and used as active substrates (Fe-MOF/glass, Fe-MOF/Au, Ni-MOF/glass and Ni-MOF/Au, respectively) for MTT cell-proliferation and reactive oxygen species tests using the PC-12 cell-line in order to investigate the biocompatibility. Immunostaining and morphological analyses of PC-12 cells on MOF interfaces suggested a stronger cell-substrate interaction in comparison to glass and were further characterized using the Electrical Cell-substrate Impedance Sensing (ECIS) technique, here for the first time, employed to study cell attachment, spreading and proliferation on 2D Fe-MOF. The 2D Fe-MOF showed superior long-term stability in cell culture medium by recording impedance over 24 hours, crucial to monitor cell-dynamics at a solid-liquid interface. A significant increase of interfacial impedance was observed in ECIS, due to PC-12 cells adhering onto 2D Fe-MOF, which was also confirmed by the focused ion beam etching followed by scanning electron microscopy. Our novel findings, therefore, suggest 2D MOFs as highly suitable platform for the study of cell-related interactions using electrical techniques and potentially pave the way for future use of MOFs for bioelectronics and biosensor applications.

Authors 14

1. Huijie Jiang Aachen Institute of Materials in Electrical Engineering 1

   RWTH Aachen University

   Affiliation as printed

   Institute of Materials in Electrical Engineering 1, RWTH Aachen University, 52074 Aachen, Germany

2. Ziyu Gao Aachen Neuroeelctronic Interfaces Teaching and Research Area

   Forschungszentrum Jülich · RWTH Aachen University

   Affiliation as printed

   Institute for Biological Information Processing – Bioelectronics, IBI-3, Forschungszentrum Jülich GmbH, 52428 Aachen, Germany

   Neuroeelctronic Interfaces Teaching and Research Area, RWTH Aachen University, 52074 Aachen, Germany

3. Claudia Lubrano Aachen Neuroeelctronic Interfaces Teaching and Research Area

   Forschungszentrum Jülich · RWTH Aachen University

   Affiliation as printed

   Institute for Biological Information Processing – Bioelectronics, IBI-3, Forschungszentrum Jülich GmbH, 52428 Aachen, Germany

   Neuroeelctronic Interfaces Teaching and Research Area, RWTH Aachen University, 52074 Aachen, Germany

4. Claudia Latte Bovio

   Italian Institute of Technology · University of Naples Federico II

   Affiliation as printed

   Dipartimento di Chimica, Materiali e Produzione Industriale, Università di Napoli Federico II, I-80125, Naples, Italy

   Tissue Electronics, Istituto Italiano di Tecnologia, I-80125 Naples, Italy

5. Henning Bommes Aachen Institute of Materials in Electrical Engineering 1

   RWTH Aachen University

   Affiliation as printed

   Institute of Materials in Electrical Engineering 1, RWTH Aachen University, 52074 Aachen, Germany

6. Andrea Kauth Aachen Institute of Materials in Electrical Engineering 1

   RWTH Aachen University

   Affiliation as printed

   Institute of Materials in Electrical Engineering 1, RWTH Aachen University, 52074 Aachen, Germany

7. Lea Baumann Aachen Institute of Materials in Electrical Engineering 1

   RWTH Aachen University

   Affiliation as printed

   Institute of Materials in Electrical Engineering 1, RWTH Aachen University, 52074 Aachen, Germany

8. Bowen Cheng Aachen Institute of Materials in Electrical Engineering 1

   RWTH Aachen University

   Affiliation as printed

   Institute of Materials in Electrical Engineering 1, RWTH Aachen University, 52074 Aachen, Germany

9. Divagar Murugan Aachen Institute of Materials in Electrical Engineering 1

   RWTH Aachen University

   Affiliation as printed

   Institute of Materials in Electrical Engineering 1, RWTH Aachen University, 52074 Aachen, Germany

10. Joachim Knoch Aachen Institute of Semiconductor Electronics

    RWTH Aachen University

    Affiliation as printed

    Institute of Semiconductor Electronics, RWTH Aachen University, 52074 Aachen, Germany

11. Rainer Waser Aachen Institute of Materials in Electrical Engineering II

    Forschungszentrum Jülich · RWTH Aachen University

    Affiliation as printed

    Institute of Materials in Electrical Engineering II, RWTH Aachen University, 52074 Aachen, Germany

    Peter-Grünberg Institut (PGI-7 and PGI-10), Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

12. Sven Ingebrandt Aachen Institute of Materials in Electrical Engineering 1

    RWTH Aachen University

    Affiliation as printed

    Institute of Materials in Electrical Engineering 1, RWTH Aachen University, 52074 Aachen, Germany

13. Francesca Santoro Aachen Neuroeelctronic Interfaces Teaching and Research Area

    Forschungszentrum Jülich · Italian Institute of Technology · RWTH Aachen University

    Affiliation as printed

    Institute for Biological Information Processing – Bioelectronics, IBI-3, Forschungszentrum Jülich GmbH, 52428 Aachen, Germany

    Neuroeelctronic Interfaces Teaching and Research Area, RWTH Aachen University, 52074 Aachen, Germany

    Tissue Electronics, Istituto Italiano di Tecnologia, I-80125 Naples, Italy

14. Vivek Pachauri corresponding Aachen Institute of Materials in Electrical Engineering 1

    RWTH Aachen University

    Affiliation as printed

    Institute of Materials in Electrical Engineering 1, RWTH Aachen University, 52074 Aachen, Germany