Kilpijärvi, J.; Halonen, N.; Sobocinski, M.; Hassinen, A.; Senevirathna, B.; Uvdal, K.; Abshire, P.; Smela, E.; Kellokumpu, S.; Juuti, J.; Lloyd Spetz, A. LTCC Packaged Ring Oscillator Based Sensor for Evaluation of Cell Proliferation. Sensors 2018, 18, 3346. https://doi.org/10.3390/s18103346
LTCC packaged ring oscillator based sensor for evaluation of cell proliferation
|Author:||Kilpijärvi, Joni1; Halonen, Niina1; Sobocinski, Maciej1;|
1Microelectronics Research Unit, University of Oulu, P.O. Box 4500, FI-90014 Oulu, Finland
2Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, FI-90014 Oulu, Finland
3Department of Electrical & Computer Engineering and the Institute for Systems Research, University of Maryland, College Park, MD 20742, USA
4Division of Molecular Surface Physics and Nanoscience, Department of Physics, Chemistry and Biology, Linköping University, SE-58183 Linköping, Sweden
5Department of Mechanical Engineering and the Institute for Systems Research, University of Maryland, College Park, MD 20742, USA
6Division of Sensor and Actuator Systems, Department of Physics, Chemistry and Biology, Linköping University, SE-58183 Linköping, Sweden
|Online Access:||PDF Full Text (PDF, 3.9 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2018101238185
Multidisciplinary Digital Publishing Institute,
|Publish Date:|| 2018-10-12
A complementary metal-oxide-semiconductor (CMOS) chip biosensor was developed for cell viability monitoring based on an array of capacitance sensors utilizing a ring oscillator. The chip was packaged in a low temperature co-fired ceramic (LTCC) module with a flip chip bonding technique. A microcontroller operates the chip, while the whole measurement system was controlled by PC. The developed biosensor was applied for measurement of the proliferation stage of adherent cells where the sensor response depends on the ratio between healthy, viable and multiplying cells, which adhere onto the chip surface, and necrotic or apoptotic cells, which detach from the chip surface. This change in cellular adhesion caused a change in the effective permittivity in the vicinity of the sensor element, which was sensed as a change in oscillation frequency of the ring oscillator. The sensor was tested with human lung epithelial cells (BEAS-2B) during cell addition, proliferation and migration, and finally detachment induced by trypsin protease treatment. The difference in sensor response with and without cells was measured as a frequency shift in the scale of 1.1 MHz from the base frequency of 57.2 MHz. Moreover, the number of cells in the sensor vicinity was directly proportional to the frequency shift.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
213 Electronic, automation and communications engineering, electronics
This work has been financially supported by the Academy of Finland (The ClintoxNP project #268944) and TEKES (The Chempack project # 1427/31/2010).
|Academy of Finland Grant Number:||
268944 (Academy of Finland Funding decision)
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).