Rapid spheroid assays in a 3-dimensional cell culture chip

Jia Lin Teh,Gregory Domnic,Nelson Jeng Yeou Chear,Siti Fairus Abdul Rahman,Lengishwarra Satiyasilan,Darshan Singh,Nethia Mohana-Kumaran

doi:10.1186/s13104-021-05727-0

Abstract

ObjectiveThe spheroid model provides a physiological platform to study cancer cell biology and drug sensitivity. Usage of bovine collagen I for spheroid assays is costly especially when experiments are conducted in 24-well plates, as high volume of bovine collagen I is needed. The aim of the study was to downsize spheroid assays to a microfluidic 3D cell culture chip and compare the growth, invasion and response to drug/compound of spheroids embedded in the 3D chip to spheroids embedded in 24-well plates.ResultsSpheroids generated from nasopharyngeal carcinoma cell line HK-1 continuously grew and invaded into collagen matrix in a 24-well plate. Similar observations were noticed with spheroids embedded in the 3D chip. Large spheroids in both 24-well plate and the 3D chip disintegrated and invaded into the collagen matrix. Preliminary drug sensitivity assays showed that the growth and invasion of spheroids were inhibited when spheroids were treated with combination of cisplatin and paynantheine at high concentrations, in a 24-well plate. Comparable findings were obtained when spheroids were treated with the same drug combination in the 3D chip. Moving forward, spheroid assays could be performed in the 3D chip in a more high-throughput manner with minimal time and cost.

Highlights

Nasopharyngeal carcinoma (NPC) manifests beneath the nasopharyngeal mucosa or within the pharyngeal recess, known as the Fossa of Rosenmüller [1, 2]
Spheroid assays conducted in the 3D chip were comparable to spheroid assays conducted in a 24‐well plate Given that this is the first time we were using the 3D chip, to perform experiments with the HK-1 spheroids, the growth and invasion of the spheroids were tested in the 24-well plate and in the 3D chip simultaneously
Quantification of relative spheroid growth area demonstrate that spheroids were viable throughout the duration of the experiment, as the spheroids grew in size to cover more area of the collagen matrix, over 7 days (Fig. 2b)

Summary

Results

Spheroid assays conducted in the 3D chip were comparable to spheroid assays conducted in a 24‐well plate Given that this is the first time we were using the 3D chip, to perform experiments with the HK-1 spheroids, the growth and invasion of the spheroids were tested in the 24-well plate and in the 3D chip simultaneously. Similar observations were noticed with spheroids embedded in the 3D chip (Fig. 2c, d) Spheroids in both the 24-well plate and the 3D chip disintegrated and invaded into the collagen matrix over time (Fig. 2a and c—see the holes in the spheroids that were not masked by the imaging software). It appears that this disintegration of cells occurred more rapidly in spheroids embedded in the 3D chip (by day 3) compared to in the 24-well plate (Fig. 2a and c). The spheroids embedded in the chip and in the 24-well plate were treated with combination a Spheroid growth and invasion in a 24-well plate

Introduction

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Discussion

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