TY - JOUR
T1 - Longitudinal Morphological and Physiological Monitoring of Three-dimensional Tumor Spheroids Using Optical Coherence Tomography
AU - Huang, Yongyang
AU - Zou, Jinyun
AU - Badar, Mudabbir
AU - Liu, Junchao
AU - Shi, Wentao
AU - Wang, Shunqiang
AU - Guo, Qiongyu
AU - Wang, Xiaofang
AU - Kessel, Sarah
AU - Chan, Leo Li Ying
AU - Li, Peter
AU - Liu, Yaling
AU - Qiu, Jean
AU - Zhou, Chao
N1 - Publisher Copyright:
© 2019 Journal of Visualized Experiments.
PY - 2019/2
Y1 - 2019/2
N2 - Tumor spheroids have been developed as a three-dimensional (3D) cell culture model in cancer research and anti-cancer drug discovery. However, currently, high-throughput imaging modalities utilizing bright field or fluorescence detection, are unable to resolve the overall 3D structure of the tumor spheroid due to limited light penetration, diffusion of fluorescent dyes and depth-resolvability. Recently, our lab demonstrated the use of optical coherence tomography (OCT), a label-free and non-destructive 3D imaging modality, to perform longitudinal characterization of multicellular tumor spheroids in a 96-well plate. OCT was capable of obtaining 3D morphological and physiological information of tumor spheroids growing up to about 600 µm in height. In this article, we demonstrate a high-throughput OCT (HT-OCT) imaging system that scans the whole multi-well plate and obtains 3D OCT data of tumor spheroids automatically. We describe the details of the HT-OCT system and construction guidelines in the protocol. From the 3D OCT data, one can visualize the overall structure of the spheroid with 3D rendered and orthogonal slices, characterize the longitudinal growth curve of the tumor spheroid based on the morphological information of size and volume, and monitor the growth of the dead-cell regions in the tumor spheroid based on optical intrinsic attenuation contrast. We show that HT-OCT can be used as a high-throughput imaging modality for drug screening as well as characterizing biofabricated samples.
AB - Tumor spheroids have been developed as a three-dimensional (3D) cell culture model in cancer research and anti-cancer drug discovery. However, currently, high-throughput imaging modalities utilizing bright field or fluorescence detection, are unable to resolve the overall 3D structure of the tumor spheroid due to limited light penetration, diffusion of fluorescent dyes and depth-resolvability. Recently, our lab demonstrated the use of optical coherence tomography (OCT), a label-free and non-destructive 3D imaging modality, to perform longitudinal characterization of multicellular tumor spheroids in a 96-well plate. OCT was capable of obtaining 3D morphological and physiological information of tumor spheroids growing up to about 600 µm in height. In this article, we demonstrate a high-throughput OCT (HT-OCT) imaging system that scans the whole multi-well plate and obtains 3D OCT data of tumor spheroids automatically. We describe the details of the HT-OCT system and construction guidelines in the protocol. From the 3D OCT data, one can visualize the overall structure of the spheroid with 3D rendered and orthogonal slices, characterize the longitudinal growth curve of the tumor spheroid based on the morphological information of size and volume, and monitor the growth of the dead-cell regions in the tumor spheroid based on optical intrinsic attenuation contrast. We show that HT-OCT can be used as a high-throughput imaging modality for drug screening as well as characterizing biofabricated samples.
KW - Cancer Research
KW - Issue 144
KW - OCT
KW - antitumor drug screening assays
KW - cellular spheroids
KW - cultured tumor cells
KW - high-throughput screening assays
KW - optical coherence tomography
KW - optical imaging
KW - three-dimensional imaging
UR - http://www.scopus.com/inward/record.url?scp=85062110210&partnerID=8YFLogxK
U2 - 10.3791/59020
DO - 10.3791/59020
M3 - Article
C2 - 30799861
AN - SCOPUS:85062110210
SN - 1940-087X
VL - 2019
JO - Journal of Visualized Experiments
JF - Journal of Visualized Experiments
IS - 144
M1 - e59020
ER -