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Related Experiment Video

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LTCC Packaged Ring Oscillator Based Sensor for Evaluation of Cell Proliferation.

Joni Kilpijärvi1, Niina Halonen2, Maciej Sobocinski3

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Sensors (Basel, Switzerland)
|October 11, 2018
PubMed
Summary

A novel complementary metal-oxide-semiconductor (CMOS) biosensor monitors cell viability by detecting changes in cell adhesion. This chip biosensor offers a sensitive method for real-time cell proliferation and detachment analysis.

Keywords:
CMOScapacitive sensingcell proliferation assaylab-on-a-chiplow temperature co-fired ceramicring oscillator

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Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Cell Biology

Background:

  • Cell viability monitoring is crucial for drug development and disease research.
  • Existing methods for cell monitoring can be complex or lack real-time capabilities.
  • Complementary metal-oxide-semiconductor (CMOS) technology offers potential for miniaturized biosensor development.

Purpose of the Study:

  • To develop a CMOS chip biosensor for real-time cell viability monitoring.
  • To investigate the relationship between cell adhesion and sensor response.
  • To assess the biosensor's performance in tracking cell proliferation and detachment.

Main Methods:

  • Fabrication of a CMOS chip biosensor with capacitance sensors and a ring oscillator.
  • Packaging the chip in a low temperature co-fired ceramic (LTCC) module using flip chip bonding.
  • Utilizing a microcontroller and PC for system operation and measurement control.
  • Testing the biosensor with human lung epithelial cells (BEAS-2B) to monitor proliferation and detachment.

Main Results:

  • The biosensor detected changes in cell adhesion, which altered effective permittivity and sensor oscillation frequency.
  • A frequency shift of 1.1 MHz from a base frequency of 57.2 MHz was observed due to cell presence.
  • The sensor response (frequency shift) was directly proportional to the number of cells near the sensor.

Conclusions:

  • The developed CMOS biosensor effectively monitors cell viability and proliferation based on cell adhesion.
  • The biosensor provides a sensitive and label-free method for real-time cell monitoring.
  • This technology has potential applications in drug screening, toxicology, and fundamental cell biology research.