TY - JOUR

T1 - Moving perfusion culture and live-cell imaging from lab to disc

T2 - proof of concept toxicity assay with AI-based image analysis

AU - Serioli, Laura

AU - Gruzinskyte, Lina

AU - Zappalà, Giulia

AU - Hwu, En Te

AU - Laksafoss, Trygvi Zachariassen

AU - Jensen, Peter Lunding

AU - Demarchi, Danilo

AU - Müllertz, Anette

AU - Boisen, Anja

AU - Zór, Kinga

N1 - Funding Information: This work was supported by the Danish National Research Foundation (DNRF122) and Villum Fonden (Grant No. 9301) for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN) and by the Novo Nordisk Foundation ‘Cell culture and On-line Monitoring Platform Anchored on Centrifugal microfluidics Technology’ (COMPACT) (Grant No. NNF21OC0069057). We also acknowledge Professor Akinobu Yamaguchi and Mr Atsushi Ishimoto from the Laboratory of Advanced Science and Technology for Industry (LASTI), University of Hyogo, Japan for their support in this work. Publisher Copyright: © 2023 The Royal Society of Chemistry.

PY - 2023

Y1 - 2023

N2 - In vitro, cell-based assays are essential in diagnostics and drug development. There are ongoing efforts to establish new technologies that enable real-time detection of cell-drug interaction during culture under flow conditions. Our compact (10 × 10 × 8.5 cm) cell culture and microscope on disc (CMoD) platform aims to decrease the application barriers of existing lab-on-a-chip (LoC) approaches. For the first time in a centrifugal device, (i) cells were cultured for up to six days while a spindle motor facilitated culture medium perfusion, and (ii) an onboard microscope enabled live bright-field imaging of cells while the data wirelessly transmitted to a computer. The quantification of cells from the acquired images was done using artificial intelligence (AI) software. After optimization, the obtained cell viability data from the AI-based image analysis proved to correlate well with data collected from commonly used image analysis software. The CMoD was also suitable for conducting a proof-of-concept toxicity assay with HeLa cells under continuous flow. The half-maximal inhibitory time (IT50) for various concentrations of doxorubicin (DOX) in the case of HeLa cells in flow, was shown to be lower than the IT50 obtained from a static cytotoxicity assay, indicating a faster onset of cell death in flow. The CMoD proved to be easy to handle, enabled cell culture and monitoring without assistance, and is a promising tool for examining the dynamic processes of cells in real-time assays.

AB - In vitro, cell-based assays are essential in diagnostics and drug development. There are ongoing efforts to establish new technologies that enable real-time detection of cell-drug interaction during culture under flow conditions. Our compact (10 × 10 × 8.5 cm) cell culture and microscope on disc (CMoD) platform aims to decrease the application barriers of existing lab-on-a-chip (LoC) approaches. For the first time in a centrifugal device, (i) cells were cultured for up to six days while a spindle motor facilitated culture medium perfusion, and (ii) an onboard microscope enabled live bright-field imaging of cells while the data wirelessly transmitted to a computer. The quantification of cells from the acquired images was done using artificial intelligence (AI) software. After optimization, the obtained cell viability data from the AI-based image analysis proved to correlate well with data collected from commonly used image analysis software. The CMoD was also suitable for conducting a proof-of-concept toxicity assay with HeLa cells under continuous flow. The half-maximal inhibitory time (IT50) for various concentrations of doxorubicin (DOX) in the case of HeLa cells in flow, was shown to be lower than the IT50 obtained from a static cytotoxicity assay, indicating a faster onset of cell death in flow. The CMoD proved to be easy to handle, enabled cell culture and monitoring without assistance, and is a promising tool for examining the dynamic processes of cells in real-time assays.

U2 - 10.1039/d2lc00984f

DO - 10.1039/d2lc00984f

M3 - Journal article

C2 - 36790123

AN - SCOPUS:85148675359

VL - 23

SP - 1603

EP - 1612

JO - Lab on a Chip

JF - Lab on a Chip

SN - 1473-0197

ER -