9 research outputs found

    Low temperature co-fired ceramic package for lab-on-CMOS applied in cell viability monitoring

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    Lab-on-CMOS chips (LOCMOS) are sophisticated miniaturized analysis tools based on integrated circuit (IC) microchips performing various laboratory functions. We have developed a low temperature co-fired ceramic (LTCC) package for a LOCMOS application regarding cytotoxicity assessment of nanomaterials. The LTCC packaged capacitance sensor chip is designed for long-term cell viability monitoring during nanoparticle exposure. The introduced LTCC package utilizes the flip chip bonding technique, and it is biocompatible as well as able to withstand the environmental conditions required to maintain mammalian cell culture directly on the surface of a complementary metal oxide semiconductor (CMOS) integrated circuit

    Low temperature co-fired ceramic packaging of CMOS capacitive sensor chip towards cell viability monitoring

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    Abstract Cell viability monitoring is an important part of biosafety evaluation for the detection of toxic effects on cells caused by nanomaterials, preferably by label-free, noninvasive, fast, and cost effective methods. These requirements can be met by monitoring cell viability with a capacitance-sensing integrated circuit (IC) microchip. The capacitance provides a measurement of the surface attachment of adherent cells as an indication of their health status. However, the moist, warm, and corrosive biological environment requires reliable packaging of the sensor chip. In this work, a second generation of low temperature co-fired ceramic (LTCC) technology was combined with flip-chip bonding to provide a durable package compatible with cell culture. The LTCC-packaged sensor chip was integrated with a printed circuit board, data acquisition device, and measurement-controlling software. The packaged sensor chip functioned well in the presence of cell medium and cells, with output voltages depending on the medium above the capacitors. Moreover, the manufacturing of microfluidic channels in the LTCC package was demonstrated

    LTCC packaged ring oscillator based sensor for evaluation of cell proliferation

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    Abstract 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
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