Silicon nanowires (SiNW) are highly sensitive to biomolecules. In some publications, changes of SiNW conductance in relation to their concentration levels are displayed. Upon binding, biomolecule charges change the surface potential and, thereby, the SiNW conductance. We discussed earlier that SiNWs can be regarded as long-channel, ion-sensitive field-effect transistors (ISFETs). The choice of a stable working point is important and defines the SiNW conductance. The common detection principle is based on the shift in threshold voltage. Regardless of conductance change or threshold voltage shift, relative values are related to biomolecule concentrations. However, potentiometric detection suffers from Debye screening of biomolecule charges by counter ions of the test solution. This makes biosensing in physiological buffer solutions difficult if not impossible. In this report, a method for impedance sensing with SiNWs, which was earlier used for ISFET devices is introduced. This method gains comparable results to potentiometric sensing. The change of interface impedance is indirectly linked with the biomolecule charges. In addition, the dielectric property of the interface layer plays an important role. At elevated frequencies, our method can be regarded as an alternative mechanism similar to dielectric spectroscopy at low frequencies. Thereby, Debye screening does no longer dominate the recordings.Nowadays, the detection of DNA is essential and indispensable in biomedicine. There are many scientific applications, in which the identification of the base pair sequence is crucial. Applications can be found in criminology, i.e., forensics, [1][2][3] determination of gene mutations in plants, [4][5][6] DNA detection in biotechnology, [7][8][9] and in the detection of different, genetically predetermined diseases in medicine. [10][11][12] Within all these applications, the possibility of a fully electronic, labelfree DNA detection is getting more and more interesting to provide a quick and reliable readout. This is especially needed in forensics to convict a perpetrator and in medicine for the fast diagnosis of diseases so that the patient can immediately be medicated or operated. Moreover, a swift DNA detection is desired for biological warfare agents. [13] Since the first publication of Piet Bergveld and coworkers in 1970, [14] ion-sensitive field-effect transistors (ISFETs) are applied as biosensors for biomolecules, such as DNA, [15][16][17][18][19] enzymes, [20][21][22] and proteins. [23][24][25] Furthermore, it was shown that it is also possible to record cellular signals with ISFETs. [26][27][28] In the past decades, the application of silicon nanowires (SiNWs) attracted more and more attention in terms of extracellular recordings [29][30][31] and biomolecule sensing, like the detection of DNA immobilization, [32] hybridization, [33] and single nucleotide polymorphism [34][35][36] as well as antibody-antigen interactions. [37,38] In an earlier publication, we discussed that our silicon nanowire devices can be rega...