The oxygen partial pressure and pH are essential parameters in microenvironment that influence the cell metabolism. Oxygen consumption due to cellular respiration is the most common approach for energy production. In addition, dysregulated extracellular pH of cancer cells is investigated to a large extent for clinical diagnosis or targeted therapy. In this work, we demonstrate the feasibility of integration of optical oxygen and pH sensors into digital microfluidic devices to perform multiple biological assays including on-chip antimicrobial susceptibility testing and anti-cancer drug screening assays.

We fabricated and applied a digital microfluidic chip integrated with optical oxygen sensor film to perform automated miniaturized antimicrobial susceptibility test by recording the extra...[ Read more ]

The oxygen partial pressure and pH are essential parameters in microenvironment that influence the cell metabolism. Oxygen consumption due to cellular respiration is the most common approach for energy production. In addition, dysregulated extracellular pH of cancer cells is investigated to a large extent for clinical diagnosis or targeted therapy. In this work, we demonstrate the feasibility of integration of optical oxygen and pH sensors into digital microfluidic devices to perform multiple biological assays including on-chip antimicrobial susceptibility testing and anti-cancer drug screening assays.

We fabricated and applied a digital microfluidic chip integrated with optical oxygen sensor film to perform automated miniaturized antimicrobial susceptibility test by recording the extracellular dissolved oxygen change caused by cellular respiration.

Here, the oxygen sensitive probe PtTFPP was embedded in a Hyflon AD60 polymer and spin coated as a 100 nm thick layer onto an ITO glass serving as the DMF ground electrode. A rapid and reliable two-fold dilution procedure was developed and performed and AST with E. coli ATCC 25922 in the presence of ampicillin, chloramphenicol and tetracycline at different concentrations from 0.5 to 8 μg mL^-1 were investigated. The minimum inhibitory concentration values measured from DMF chip were consistent with that from the standard broth microdilution method but requiring only minimal sample handling and working with much smaller sample volumes.

Lastly, extracellular pH monitoring of adherent cancer cell cultures on the DMF chip is demonstrated. FITC was covalently linked to pHEMA and localized immobilized on a circular exposed hydrophilic site on DMF top plate via passive dispending. The working range of the pH sensor spot was pH 4.8 to pH 7.8 which was suitable for pH measurement in cell culture medium.

Polydopamine was added as a cell adhesion promotor on the pH sensor surface. The sensitivity of the pH sensor was not affected by this modification. Luminescence-based pH sensor films can measure the acidification process of cancer cell metabolism due to the abnormal excess glycolysis. The results showed that the extracellular pH change of cancer cells (breast cancer MCF-7 and lung cancer A549) was significantly larger than normal cells (HUVEC). Based on this, we further investigated the effect of glucose concentration and the anti-cancer drug dexamethasone on cancer cell acidification. PL intensity decreasing rate illustrated the cancer cell acidification rate increased at high glucose level. However, the rate decreased under 0.1 μg mL^-1 dexamethasone stimulation. Here, we present the first digital microfluidic platform integrated with optical pH sensors for probing the extracellular pH change of cancer cells and anti-cancer drug screening.