Accurate Nanoliter Liquid Characterization Up to 40 GHz for Biomedical Applications: Toward Noninvasive Living Cells Monitoring

This paper demonstrates an accurate liquid sensing technique, from 40 MHz to 40 GHz, which is suitable for the detection and quantification of very small contents of molecules, proteins, and for the noninvasive and contactless microwave investigation of living cells in their culture medium. The sensor is based on an interdigitated capacitor (IDC) with a microfluidic channel to confine the nanoliter-range liquid and is integrated with microtechnologies to be fully compatible with a massive parallelization at low cost. Both alcohol and biological aqueous solutions are precisely characterized, identified, and quantified in terms of capacitance and conductance's contrasts with respect to pure de-ionized water. Mixtures from 20% down to 1% of ethanol in water exhibit large capacitance's values of 110 and 7 fF at 11 GHz, respectively. Based on the high accuracy of such characterizations, the detection of very small traces of ethanol (down to 100 ppm) can be envisioned. As far as biomedical applications are targeted, we also demonstrate the potential of fetal bovine serum detection in aqueous solution down to 5% v/v. Finally, the sensor is evaluated with living B lymphoma cells suspension in their traditional biological medium. The in-liquid microwave measurement of less than 20 living cells is successfully performed and corresponds to a capacitance contrast of 5 fF at 3 GHz relative to the reference bio-medium. For low cells concentration, the sensor response is proportional to the number of cells on the IDC, which permits to envision cells quantification and proliferation monitoring with this microwave sensing technique.