Microfluidic chip system integrated with light addressable potentiometric sensor (LAPS) for real-time extracellular acidification detection

Metabolism is a common biological mechanism in living cells. Acidification plays an important role in cell metabolism, in which the extracellular pH change is used to indicate the vitality of cells. For extracellular detection of cell metabolic substances, light addressable potentiometric sensor (LAPS) has many advantages, such as high sensitivity, easy encapsulation, and convenient integration with microfluidic system for cell experiments. LAPS is a spatially resolved biochemical sensor based on field-effect. In this work, we present a microfluidic system integrated with LAPS for real-time extracellular acidification rate (ECAR) detection. The functions of traditional microphysiometer are achieved with simpler structure devices. Polydimethylsiloxane (PDMS) chamber was manufactured for cell culture, and microfluidic flow paths were used for medium and drug delivery. A bubble trap device was applied to eliminate air bubbles generated in microfluidics. Characteristic tests and cell metabolism experiments were carried out to determine the performance of LAPS by monitoring the pH change of hepatoma HepG2 cells. Glucose and doxorubicin were delivered to the cell chamber to verify the effects of the drug. The pH sensitivity of LAPS is 335.5 nA/pH at the working point in constant voltage mode. The ECAR of HepG2 cells was -48.53 mpH/min in normal glucose medium (25 mM), and it changed to -114.42 mpH/min in high glucose medium (125 mM) and -17.88 mpH/min under the effect of doxorubicin (10 mu M). The results show that the microfluidic LAPS presents good performance in real-time detection of cell acidification and provides a convenient means of assessing cellular specificity of drugs. The modular structure and high expandability make the microfluidic LAPS has good potential in the application of organ-on-chip.