Disclosed are systems and methods for monitoring biopotential signals in biomedical devices. The disclosure provides a mixed signal background calibration that stabilizes the time-varying coupling gain between the body and an electrode due to motion artifacts. The calibration technique involves a low-level test signal in the form of a one-bit pseudorandom bit-sequence that is injected through a reference electrode to the body, detected by the sensing electrode and recorded along with the bio signals. A digital algorithm is employed in the backend to identify the acquisition channel characteristics while maintaining its normal operation of recording. Programmable gain stages in analog or digital domain(s) can be used to stabilize the overall gain of the channel. The disclosed technique is in the background and not interfering with the normal recording operation(s), and provides continuous monitoring of the ETI and continuous correction of the ensuing channel characteristic degradation due to the ETI variation.