Biocompatibility characterisation of CMOS-based Lab-on-Chip electrochemical sensors for in vitro cancer cell culture applications.

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Authors

Beykou, M
Bousgouni, V
Moser, N
Georgiou, P
Bakal, C

Document Type

Journal Article

Date

2024-10-15

Date Accepted

2024-06-17

Date Available

2024-09-13T14:52:28Z

Abstract

Lab-on-Chip electrochemical sensors, such as Ion-Sensitive Field-Effect Transistors (ISFETs), are being developed for use in point-of-care diagnostics, such as pH detection of tumour microenvironments, due to their integration with standard Complementary Metal Oxide Semiconductor (CMOS) technology. With this approach, the passivation of the CMOS process is used as a sensing layer to minimise post-processing, and Silicon Nitride (Si3N4) is the most common material at the microchip surface. ISFETs have the potential to be used for cell-based assays however, there is a poor understanding of the biocompatibility of microchip surfaces. Here, we quantitatively evaluated cell adhesion, morphogenesis, proliferation and mechano-responsiveness of both normal and cancer cells cultured on a Si3N4, sensor surface. We demonstrate that both normal and cancer cell adhesion decreased on Si3N4. Activation of the mechano-responsive transcription regulators, YAP/TAZ, are significantly decreased in cancer cells on Si3N4 in comparison to standard cell culture plastic, whilst proliferation marker, Ki67, expression markedly increased. Non-tumorigenic cells on chip showed less sensitivity to culture on Si3N4 than cancer cells. Treatment with extracellular matrix components increased cell adhesion in normal and cancer cell cultures, surpassing the adhesiveness of plastic alone. Moreover, poly-l-ornithine and laminin treatment restored YAP/TAZ levels in both non-tumorigenic and cancer cells to levels comparable to those observed on plastic. Thus, engineering the electrochemical sensor surface with treatments will provide a more physiologically relevant environment for future cell-based assay development on chip.

Citation

Biosensors and Bioelectronics, 2024, 262 pp. 116513 -

Source Title

Biosensors and Bioelectronics

Publisher

ELSEVIER ADVANCED TECHNOLOGY

ISSN

0956-5663

eISSN

1873-4235
1873-4235

Collections

Research Team

Dynamical Cell Systems

Notes