Automated fabrication of a scalable heart-on-a-chip device by 3D printing of thermoplastic elastomer nanocomposite and hot embossing

Qinghua Wu; Ruikang Xue; Yimu Zhao; Kaitlyn Ramsay; Erika Yan Wang; Houman Savoji; Teodor Veres; Sarah H Cartmell; Milica Radisic

doi:10.1016/j.bioactmat.2023.10.019

Automated fabrication of a scalable heart-on-a-chip device by 3D printing of thermoplastic elastomer nanocomposite and hot embossing

Bioact Mater. 2023 Nov 7:33:46-60. doi: 10.1016/j.bioactmat.2023.10.019. eCollection 2024 Mar.

Authors

Qinghua Wu^{1

2}, Ruikang Xue³, Yimu Zhao², Kaitlyn Ramsay¹, Erika Yan Wang⁴, Houman Savoji^{5

6

7}, Teodor Veres^{8

9}, Sarah H Cartmell³, Milica Radisic^{1

2

10

11}

Affiliations

¹ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9, Canada.
² Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 2C4, Canada.
³ Department of Materials, School of Natural Sciences, Faculty of Science and Engineering and The Henry Royce Institute, Royce Hub Building, The University of Manchester, Manchester, UK.
⁴ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁵ Institute of Biomedical Engineering and Department of Pharmacology and Physiology, University of Montreal, Montreal, Quebec, H3T 1J4, Canada.
⁶ Research Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, H3T 1C5, Canada.
⁷ Montreal TransMedTech Institute, Montreal, Quebec, H3T 1J4, Canada.
⁸ National Research Council of Canada, Boucherville, QC, J4B 6Y4, Canada.
⁹ Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, M5S 3G8, Canada.
¹⁰ Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5, Canada.
¹¹ Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada.

Abstract

The successful translation of organ-on-a-chip devices requires the development of an automated workflow for device fabrication, which is challenged by the need for precise deposition of multiple classes of materials in micro-meter scaled configurations. Many current heart-on-a-chip devices are produced manually, requiring the expertise and dexterity of skilled operators. Here, we devised an automated and scalable fabrication method to engineer a Biowire II multiwell platform to generate human iPSC-derived cardiac tissues. This high-throughput heart-on-a-chip platform incorporated fluorescent nanocomposite microwires as force sensors, produced from quantum dots and thermoplastic elastomer, and 3D printed on top of a polystyrene tissue culture base patterned by hot embossing. An array of built-in carbon electrodes was embedded in a single step into the base, flanking the microwells on both sides. The facile and rapid 3D printing approach efficiently and seamlessly scaled up the Biowire II system from an 8-well chip to a 24-well and a 96-well format, resulting in an increase of platform fabrication efficiency by 17,5000-69,000% per well. The device's compatibility with long-term electrical stimulation in each well facilitated the targeted generation of mature human iPSC-derived cardiac tissues, evident through a positive force-frequency relationship, post-rest potentiation, and well-aligned sarcomeric apparatus. This system's ease of use and its capacity to gauge drug responses in matured cardiac tissue make it a powerful and reliable platform for rapid preclinical drug screening and development.

Keywords: Additive manufacturing; Cardiomyocyte; Drug testing; Electrical stimulation; Heart-on-a-chip.

Grants and funding

R01 HL076485/HL/NHLBI NIH HHS/United States