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We herein demonstrate the first 96-well plate platform to screen effects of micro- and nanotopographies on cell growth and proliferation. Existing high-throughput platforms test a limited number of factors and are not fully compatible with multiple types of testing and assays. This platform is compatible with high-throughput liquid handling, high-resolution imaging, and all multiwell plate-based instrumentation. We use the platform to screen for topographies and drug-topography combinations that have short- and long-term effects on T cell activation and proliferation. We coated nanofabricated "trench-grid" surfaces with anti-CD3 and anti-CD28 antibodies to activate T cells and assayed for interleukin 2 (IL-2) cytokine production. IL-2 secretion was enhanced at 200 nm trench width and >2.3 μm grating pitch; however, the secretion was suppressed at 100 nm width and <0.5 μm pitch. The enhancement on 200 nm grid trench was further amplified with the addition of blebbistatin to reduce contractility. The 200 nm grid pattern was found to triple the number of T cells in long-term expansion, a result with direct clinical applicability in adoptive immunotherapy.

Original publication

DOI

10.1021/acs.nanolett.5b04364

Type

Journal article

Journal

Nano Lett

Publication Date

13/04/2016

Volume

16

Pages

2198 - 2204

Keywords

High-throughput screening, Lck, T cell, interleukin-2, long-term expansion, nanotechnology, Animals, Cell Culture Techniques, Humans, Interleukin-2, Lymphocyte Activation, Nanotechnology, T-Lymphocytes