Dynamic pH fluctuations in cancer cells on CMOS-based Lab-on-Chip ISFET arrays

Early diagnosis of cancer is a key avenue to improving cancer incidence rates and prognosis. This paper presents a rapid assay for live, mammalian cancer cell culture on a Lab-on-Chip ISFET array fabricated in CMOS technology. Detection of osteosarcoma cells is recorded as a significant difference in endpoint $\mathbf{p H}$ on ISFET sensors. Control measurements of $\mathbf{p H}$ change in cell culture media due to any CO<inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> supply fluctuations in an incubator allow compensation of non-ideal effects including sensor drift and baseline $\mathbf{p H}$ change associated with a bicarbonate buffering system. Distinguishing metrics, including total drift rate and standard deviation of sensor output are extracted and attributed to cell presence on-chip. Mean total drift rate shows an 89.7% difference between sample and control wells, aiding characterisation of cancer cell presence. Standard deviation captures the noise output attributed to cell culture on the sensor surface, reporting an $\mathbf{8 1. 4 \%}$ difference between populations. This Point-of-Care diagnostic device and assay for rapid cell detection on a Lab-on-Chip shows significant potential to provide a rapid and cost-effective diagnostic tool for live cell measurements.