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Nowadays, the concept of the so-called ‘self-powered’ electrochemical (bio)sensors, which don’t require external energy sources, is of great interest. Such sensors are able to wake-up only in the presence of analyte and generate power sufficient for low voltage electronics. We report on the principle of Prussian Blue-based (bio)sensors operation in power generation mode. Prussian Blue (PB) is known to be the most advantageous low-potential hydrogen peroxide transducer for both the purposes of hydrogen peroxide detection and oxidases-based sensors operation [1]. The PB-based amperometric sensors are commonly used at the working potential adjusted to 0 V (vs. Ag/AgCl/0.1 M KCl). Short-circuiting the PB-modified working electrode with the silver chloride reference electrode (inc. through the ammeter), that is possible to set the working electrode potential about 0 V without potentiostat. Generated current linearly depends on the hydrogen peroxide concentration from 2·10^-7 to 1·10^-3 M. The sensors display advantageous performance characteristics in terms of high sensitivity – 0.65 A·M^-1·cm^-2. Sensor selectivity in power generation mode exceeds two orders of magnitude allowing detection of H2O2 by its reduction in the presence of oxygen. Besides, Prussian Blue-based sensors in power generation mode retain high selectivity relatively to reductants (paracetamol, ascorbate) practically avoiding their influence on analysis. Moreover, the noise of Prussian Blue-based sensors in power generation mode is an order of magnitude lower compared to the one in a conventional three-electrode regime even in batch cell upon stirring. In turn, in three-electrode constant potential experiments the output noise is generated by operational amplifiers enhancing noises from their inputs (inc. voltage generator and feedback control amplifier). The principle was adopted for the Prussian Blue-based glucose and lactate biosensors. Prussian Blue-based glucose sensors were shown to be applicable as test-strips for the whole blood glucose analysis with coulometric detection. For more than 20 blood samples the Pearson correlation coefficient with the standard method has reached the value of 0.96, which clearly shows the validity of Prussian Blue-based biosensors in power generation mode for analysis of real samples, such complex ones as the whole undiluted blood. To sum up, Prussian Blue-based (bio)sensors successfully operate without a potentiostat by a simple short-circuiting the working and the reference electrode, thereby, the use of Prussian Blue modified electrodes in power generation mode may simplify elaboration of the controlling potentiostat. The achieved noiseless performances of Prussian Blue based (bio)sensors in power generation mode would have a potential for low voltage read-out methods, for example for printable electronics or wearable smart devices. Financial support through Russian Science Foundation grant # 16-13-00010 is greatly acknowledged. 1. A.A. Karyakin, Prussian Blue and its analogues: Electrochemistry and analytical applications. Electroanalysis, 2001. 13(10): p. 813-819.