Monolithic integration of silicon and polymer microstructures for Organ-on-Chip applications

Research output: ThesisDissertation (TU Delft)

1 Downloads (Pure)

Abstract

Drug development is a complex, time-consuming (10 - 15 years) and expensive process. For a new medicine to reach the market, the net expenses covered by the pharmaceutical industry have been estimated to be around $2.6 billion. Nevertheless, the risk of finding adverse effects or toxicity cases once the drug is already on the market is still high. Thus, pharmaceutical companies have been keenly looking forward to means to eliminate this at an early stage of the development process. Recently, Organs-on-Chips (OOCs) emerged as a potential alternative to traditional drug screening. These devices, promise, in the middle-term, to enhance the in vitro screening and, in the long term, to reduce and eventually eliminate animal models in safety and efficacy essays. Nevertheless, the fabrication methods for most of these devices are hardly adaptable to scalable fabrication processes for in vitro screening application, as they rely strongly on manual techniques. This thesis demonstrates the successful development of diverse microstructures for Organ-on-Chip applications by using scalable IC and MEMS-based fabrication techniques. Chapter 3 demonstrates the development of microfabricated porous PDMS membranes for barrier modelling. A simple and reproducible method to fabricate and transfer porous PDMS membranes with a high control on pore size, porosity, thickness, is shown. Very thin (thickness <10 ¹m) porous membranes with small features sizes down to 2 ¹mand porosity up to 65% can thus be fabricated and successfully transferred with high reproducibility. The presented results on cell transmigration, topology and barrier formation demonstrated the biocompatibility of the porous PDMS membranes. Chapter 4 shows further efforts towards the realization of manufacturable OOCs. A monolithically microfabricated OOC device, an alternative to the available devices capable to address many more applications, was demonstrated. Preliminary biological experiments indicate its biocompatibility as cells (HUVEC, Cardyomyocites) are successfully cultured and maintained viable in the microchannels and the silicon cavity. Finally, Chapter 5 demonstrates other possibilities allowed by the use of IC and MEMS techniques. The integration of microstructures that enable transduction mechanisms to monitor the cell microenvironment, is shown. Specifically, strain gauges for stress sensing as an alternative to monitor in situ strain in microfabricated OOCs, are presented. Relative resistance changes of approximately 0.008% and 1.2% for titanium and polymeric strain gauges have been observed, respectively. The technological advances shown in this thesis form a significant contribution towards manufacturable fabrication of Organs-on-Chips and the standardization of OOCs as routinely used tools for drug development.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Delft University of Technology
Supervisors/Advisors
  • Sarro, P.M., Supervisor
Thesis sponsors
Award date8 Jul 2019
Print ISBNs978-94-6384-051-4
DOIs
Publication statusPublished - 2019

Keywords

  • Organ-on-Chip
  • MEMS
  • Silicon
  • PDMS
  • Membranes
  • Cell
  • Strain
  • Stress

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  • Research Output

    • 3 Conference contribution
    • 2 Article
    • 1 Conference article
    • 1 Patent

    A novel method to transfer porous PDMS membranes for high throughput Organ-on-Chip and Lab-on-Chip assembly

    Quiros-Solano, W. F., Gaio, N., Silvestri, C., Arik, Y. B., Stassen, O. M. J. A., van der Meer, A. D., Bouten, C. V. C., van den Berg, A., Dekker, R. & Sarro, P. M., 2018, 2018 IEEE Micro Electro Mechanical Systems, MEMS 2018. Piscataway, NJ: IEEE, Vol. 2018-January. p. 318-321 4 p.

    Research output: Chapter in Book/Conference proceedings/Edited volumeConference contributionScientificpeer-review

    Open Access
    File
  • 5 Downloads (Pure)

    Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips

    Quirós-Solano, W. F., Gaio, N., Stassen, O. M. J. A., Arik, Y. B., Silvestri, C., Van Engeland, N. C. A., Van der Meer, A., Passier, R., Sahlgren, C. M., Bouten, C. V. C., van den Berg, A., Dekker, R. & Sarro, P. M., 2018, In : Scientific Reports. 8, p. 1-11 11 p., 13524.

    Research output: Contribution to journalArticleScientificpeer-review

    Open Access
    File
  • 6 Citations (Scopus)
    55 Downloads (Pure)

    Versatile 3D Stretchable Micro-Environment for Organ-on-Chip Devices Fabricated with Standard Silicon Technology

    Gaio, N. & Quiros Solano, W., 2018, IPC No. B01L, Priority date 25 Jul 2016, Priority No. WO 2018021906 A1

    Research output: Patent

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