Monitoring biochemical reactions using Y-cut quartz thermal sensors

In this paper, we present a micromachined Y-cut quartz resonator based thermal sensor array which is configured with a reaction chamber that is physically separated but located in close proximity to the resonator for sensitive calorimetric biosensing applications. The coupling of heat from the reaction chamber to the quartz resonator is achieved via radiation and conduction through ambient gas. The sensor was packaged onto a 300 mu m thick stainless plate with an opening in the middle. The sensor array was aligned to the opening and mounted from the underside of the plate. A reaction chamber designed for performing (bio)chemical reactions was used in the measurements. This configuration of the sensor allows for a very robust sensing platform with no fouling of the sensor surface or degradation in its performance metrics. Impedance-based tracking of resonance frequency was used for chemical, enzymatic, and cellular activity measurements. The sensor described has an impedance sensitivity of 852 Omega degrees C-1 or a frequency sensitivity of 7.32 kHz degrees C-1 for the 91 MHz resonator used in this work. Results on exothermic reaction between hydrochloric acid and ammonium hydroxide, the hydrolysis reaction of urea by urease and the catalytic reaction of glucose with glucose dehydrogenase are reported. From the signal to noise ratio analysis of the glucose sensor, <10 mu M glucose sensitivity could be obtained improving the detection limit by a factor of 250 in comparison to our previous work using thermopile sensors. Finally, calcium ionophore induced cellular activity was measured in pancreatic cancer cells using the sensor.