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LTCC Packaged Ring Oscillator Based Sensor for Evaluation of Cell Proliferation
Univ Oulu, Finland.
Univ Oulu, Finland.
Univ Oulu, Finland.
Univ Oulu, Finland.
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2018 (English)In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 18, no 10, article id 3346Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI , 2018. Vol. 18, no 10, article id 3346
Keywords [en]
capacitive sensing; cell proliferation assay; CMOS; lab-on-a-chip; low temperature co-fired ceramic; ring oscillator
National Category
Textile, Rubber and Polymeric Materials
Identifiers
URN: urn:nbn:se:liu:diva-152824DOI: 10.3390/s18103346ISI: 000448661500174PubMedID: 30301258OAI: oai:DiVA.org:liu-152824DiVA, id: diva2:1265234
Note

Funding Agencies|Academy of Finland [268944]; TEKES [1427/31/2010]

Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2019-03-07

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