Organ-on-a-chip devices have opened up new possibilities to accelerate the drug discovery process in a cost-efficient manner than the traditional screening methods currently deployed in the pharmaceutical industry. Using patient-derived cells and organoids, these biomimetic microfluidic devices offer a precisely controlled microenvironment that can closely mimic the patient organ’s responses to drug treatment. As a result, patient-specific drugs can rapidly be screened and allows for a “personalized” treatment. If successfully implemented, the era of precision medicine could soon become a reality. However, a massively parallel configuration of organ-on-a-chip devices in a highly automated biofactory-like setting can be highly vulnerable to external or internal manipulations. As a potential scenario, the pressure, temperature, CO2 level or flow rates of cell perfusion could be manipulated or alternatively, the experimental data manipulated or even stolen in the cyberspace. In view of such vulnerability, it would be highly advisable to come up with a more secure design of microfluidic chips that is less prone to manipulation by emulating the innate immune response of the human body. To create such a responsive system, multiple autonomous biosensors can be embedded into the organ-on-a-chip devices that sense the microenvironment continuously and notify if there are any unusual changes beyond threshold values. In this talk, the state of the art in organ-on-a-chip technology will be presented along with several implantable biosensors that could sense and actuate “immune responses” on-chip and finally, strategies how to respond to intentional manipulations discussed.