期刊
LAB ON A CHIP
卷 18, 期 2, 页码 304-314出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7lc00970d
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类别
资金
- NSERC [RGPIN-06409]
- Cancer Research Society
- CMC Microsystems
- Fond de Recherche du Quebec - Sante (FRQS)
- FRQ-NT Quebec-India post-doctoral fellowship
- FRQ-NT
- FRQ-NT graduate fellowship [185159]
- MITACS/Institute du Cancer post-doctoral fellowship
We present a microfluidic platform for automatic multi-size spheroid formation within constant volume hanging droplets (HDs) from a single inlet loading of a constant cell concentration. The platform introduces three technological improvements over the existing spheroid formation platforms: 1) cell seeding control is achieved by enrichment of a cell solution rather than dilution; 2) cell seeding in each HD is fully independent and pre-programmable at the design stage; 3) the fabricated chip operates well using a hydrophobic PDMS surface, ensuring long-term storage possibility for device usage. Pre-programmed cell seeding densities at each HD are achieved using a microfluidic funnel layer, which has an array of cone-shaped wells with increasing apex angles acting as a metering unit. The integrated platform is designed to form, treat, stain, and image multi-size spheroids on-chip. Spheroids can be analyzed on-chip or easily transferred to conventional well plates for further processing. Empirically, enrichment factors up to 37x have been demonstrated, resulting in viable spheroids of diameters ranging from 230-420 mu m and 280-530 mu m for OV90 and TOV112D cell lines, respectively. We envision that microfluidic funnels and single inlet multi-size spheroid (SIMSS) chips will find broad application in 3D biological assays where size-dependent responses are expected, including chemoresponse assays, photodynamic therapy assays, and other assays involving drug transport characterization in drug discovery.
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