Monolithic integration of a smart temperature sensor on a modular silicon-based organ-on-a-chip device

Monolithic integration of a smart temperature sensor on a modular silicon-based organ-on-a-chip device

Martins Da Ponte, R. (TU Delft Bio-Electronics)
Gaio, N. (TU Delft Electronic Components, Technology and Materials; BIOND Solutions B.V.)
van Zeijl, H.W. (TU Delft Electronic Components, Technology and Materials)
Vollebregt, S. (TU Delft Electronic Components, Technology and Materials)
Dijkstra, Paul (Philips Innovation Services)
Dekker, R. (TU Delft Electronic Components, Technology and Materials; Philips Research)
Serdijn, W.A. (TU Delft Bio-Electronics)
Giagka, Vasiliki (TU Delft Bio-Electronics; Fraunhofer Institute for Reliability and Microintegration IZM)

2021

One of the many applications of organ-on-a-chip (OOC) technology is the study of biological processes in human induced pluripotent stem cells (iPSCs) during pharmacological drug screening. It is of paramount importance to construct OOCs equipped with highly compact in situ sensors that can accurately monitor, in real time, the extracellular fluid environment and anticipate any vital physiological changes of the culture. In this paper, we report the co-fabrication of a CMOS smart sensor on the same substrate as our silicon-based OOC for real-time in situ temperature measurement of the cell culture. The proposed CMOS circuit is developed to provide the first monolithically integrated in situ smart temperature-sensing system on a micromachined silicon-based OOC device. Measurement results on wafer reveal a resolution of less than ±0.2 °C and a nonlinearity error of less than 0.05% across a temperature range from 30 to 40 °C. The sensor's time response is more than 10 times faster than the time constant of the convection-cooling mechanism found for a medium containing 0.4 ml of PBS solution. All in all, this work is the first step towards realizing OOCs with seamless integrated CMOS-based sensors capable to measure, in real time, multiple physical quantities found in cell culture experiments. It is expected that the use of commercial foundry CMOS processes may enable OOCs with very large scale of multi-sensing integration and actuation in a closed-loop system manner.

CMOS monolithic integration
MEMS
MEMS-electronics co-fabrication
Organs-on-a-chip
Smart temperature sensor
Time-mode domain signal processing

http://resolver.tudelft.nl/uuid:c6e140f2-1877-4714-963b-b7cb4baa1743

https://doi.org/10.1016/j.sna.2020.112439

0924-4247

Sensors and Actuators A: Physical: an international journal devoted to research and development of physical and chemical transducers, 317, 1 - 7

Institutional Repository

journal article

© 2021 R. Martins Da Ponte, N. Gaio, H.W. van Zeijl, S. Vollebregt, Paul Dijkstra, R. Dekker, W.A. Serdijn, Vasiliki Giagka