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One of the most recent and exciting applications for CMOS image sensors is in the biomedical field. In such applications, these sensors often operate in harsh environments (high intensity, high pressure, long time exposure), which increase the probability for the occurrence of hot pixel defects over their lifetime. This paper presents a novel smart CMOS image sensor integrating hot pixel correcting readout circuit to preserve the quality of the captured images. With this approach, no extra non-volatile memory is required in the sensor device to store the locations of the hot pixels. In addition, the reliability of the sensor is ensured by maintaining a real-time detection of hot pixels during image capture.