An instrument-on-chip for impedance measurements on nanobiosensors with attoFarad resoution

Impedance measurements play a fundamental role in biotechnology, serving both as an investigation tool and as a direct detection technique. Tracking impedance over time is extensively used for spatial monitoring, imaging, counting, sizing (Coulter counter) and sorting cells (flow cytometry) both in macro and microfluidic systems [1]. Other than cellular biology, impedance measurements are largely used also in molecular biology to operate affinity molecular biosensors [2], where impedance measurements are used to detect the binding of a target molecule to highly specific biological macromolecules such as antibodies, receptors, enzymes and DNA strands. Downscaling these systems to nanoscale dimensions would offer tremendous advantages as compared to the currently existing macro and microscale counterparts on three essential aspects, namely sensitivity (detection of single molecule binding events), response time (more efficient diffusion of the analyte) and amount of sample analyte [3]. Monitoring single molecules implies very small absolute impedance variations, on the order of a few attoFarads for the capacitive term, which should be detected by applying only a few tens of millivolts to avoid stressing the macromolecule with high electrical fields.