High-throughput fabrication of cell spheroids with 3D acoustic assembly devices

Tingkuan Miao; Keke Chen; Xiaoyun Wei; Beisi Huang; Yuecheng Qian; Ling Wang; Mingen Xu

doi:10.18063/ijb.733

High-throughput fabrication of cell spheroids with 3D acoustic assembly devices

Int J Bioprint. 2023 Apr 17;9(4):733. doi: 10.18063/ijb.733. eCollection 2023.

Authors

Tingkuan Miao¹, Keke Chen^{1

2}, Xiaoyun Wei^{1

2}, Beisi Huang¹, Yuecheng Qian¹, Ling Wang^{1

2}, Mingen Xu^{1

2}

Affiliations

¹ School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China.
² Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, China.

Abstract

Acoustic cell assembly devices are applied in cell spheroid fabrication attributed to their rapid, label-free and low-cell damage production of size-uniform spheroids. However, the spheroids yield and production efficiency are still insufficient to meet the requirements of several biomedical applications, especially those that require large quantities of cell spheroids, such as high-throughput screening, macro-scale tissue fabrication, and tissue repair. Here, we developed a novel 3D acoustic cell assembly device combined with a gelatin methacrylamide (GelMA) hydrogels for the high-throughput fabrication of cell spheroids. The acoustic device employs three orthogonal piezoelectric transducers that can generate three orthogonal standing bulk acoustic waves to create a 3D dot-array (25 × 25 × 22) of levitated acoustic nodes, enabling large-scale fabrication of cell aggregates (>13,000 per operation). The GelMA hydrogel serves as a supporting scaffold to preserve the structure of cell aggregates after the withdrawal of acoustic fields. As a result, mostly cell aggregates (>90%) mature into spheroids maintaining good cell viability. We further applied these acoustically assembled spheroids to drug testing to explore their potency in drug response. In conclusion, this 3D acoustic cell assembly device may pave the way for the scale-up fabrication of cell spheroids or even organoids, to enable flexible application in various biomedical applications, such as high-throughput screening, disease modeling, tissue engineering, and regenerative medicine.

Keywords: Acoustic cell assembly; Cell spheroids; Drug screening; High-throughput fabrication; Levitated acoustic nodes.