We have developed a reusable piezoelectric sensor that enables rapid characterization of cell viability and response to cell-affecting agents. This is accomplished via a novel polymer transduction principle that involves reaction of a pH-sensitive amphoteric polymer with metabolically generated acid. Subsequent adhesion of the protonated polymer to the transducer surface causes a decrease in the sensor resonant frequency corresponding to the cell metabolic rate. This disclosure provides the first example of a piezoelectric sensor capable of detecting metabolic responses of viable cells. The sensor provides real-time measurement of cell metabolism and division rates, and antibiotic sensitivity. This technology provides the basis for an advanced piezoelectric sensor that does not require immobilized biological receptors and can be miniaturized without compromising signal-to-noise factors.

Piezoelectric AT-cut quartz resonators immersed in aqueous media, coated with cross-linked films of the random copolymer -{ 1), exhibit large frequency changes when the pH is changed in the vicinity of the isoelectric point of the polymer film. The frequency changes are attributed to changes in the viscoelastic properties of the films that occur during phase transitions between the isoelectric form and the cationic polymer (l-NMe2H+) present at low pH or the anionic polymer (1-C02") present at high pH. These phase transitions are accompanied by dramatic changes in acoustic energy attenuation, film thickness changes, and film surface energy, as indicated by acoustic impedance analysis, phase measurement interferometric microscopy, and contact angle measurements. The results are consistent with pH-dependent segregation of the isolectric and ionic phases within the bulk and between the bulk and the surface. The unique pH-sensing capabilities of the coated resonators, combined with their robustness, ease of fabrication, and low cost, provide a convenient approach for the measurement of "threshold" pH changes. Real-time measurements of enzymatic activity and microbe metabolism are demonstrated as examples of potential applications of these sensors.

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