## 2 Description and Challenges of a Customized Biomedical Implantable Device
### Research Challenges in Implantable Devices  
The new generation of implantable devices must overcome some main barriers at its conception stage as for example: size, energy available, power dissipation, power management, signal processing, communication of the measured data, bio-compatibility, chip-level integration, packaging, bioethics, and biosecurity [37]. A conceptual body map of commercial and in development phase implantable sensors is depicted in Figure 1, focussed on the most relevant disease processes based on [PERSON] _et al_. [16]. Figure 1: Mapping of implantable devices (based on [16]). There are very interesting implementations that combine ASICs, MEMS, and the design of integrated antennas for the RF powering of the system and the telemetry of the data, based on a link between external and internal coils. A fully wireless implantable cardiovascular pressure sensing system was developed by [PERSON] _et al._[38], combining a 130-nm technology and a MEMS capacitive sensor, powering the system through an external 35-dB-m RF powering at 3.7-GHz, with a distance range up to 10 cm inside the body, with a telemetry capability of 42.2 kb/s of channel data-rate, operating at 2.4-GHz and with a medical stent of 3 cm long. [PERSON] _et al._[39] have also developed another interesting application regarding cardiovascular problems, where an implantable wireless system for monitoring hypertension is presented. The capacitive sensor, which is based on a MEMS implementation in a metal capsule, and the electronics (ASIC), forms a tip of 20 cm that will be placed in the femoral artery. In this case, the telemetry and powering is fixed at 133-kHz, with a maximum distance of 10 cm. In [PERSON] _et al._[40], a bladder-pressure-sensing implantable for chronic patients is introduced, based on a specific ASIC design, and also based on a RF powering (LC coupling at 3-MHz), and telemetry solution, but operating in an unlicensed ISM band (27.12-MHz), and a rechargeable battery solution. In this case, the size is also based on medical constraints given by minimally invasive cystoscopic surgery, defining a final capsule of 7-mm wide by 4-mm thick by 15-mm long. Another interesting implementation is related to glaucoma [41]. In this case, an RF intraocular pressure monitor is implemented based also in a MEMS solution for the sensor and in RF wireless transmission at 2.4-GHz and RF powering operating at 3.65-GHZ. In this way, RF powering and telemetry path are isolated in the same way as in the other examples. An additional approach is presented in [PERSON] _et al._[42], where RF powering and biomedical telemetry at 1.8-GHz are combined with the aim of developing a locomotive implantable. Other interesting examples for close-loop systems are presented in [17, 43, 44]. [PERSON] _et al._[43] developed an implantable drug delivery system for the treatment of refractory epilepsy. The system is able to acquire real-time epileptic detection with focal antiepileptic drug injection feedback, combining electronics, pumps, reservoirs, _etc._ [PERSON] _et al._[17] presented an implantable microstimulator applied in a closed-loop cardiac pacemaker. [PERSON] _et al._[44] reported a fully intraocular epiretinal prosthesis, based on a 65 nm CMOS ASIC with 512 independent channels, integrated with a flexible MEMS origami coils, for the inductive powering at 10-MHz, and telemetry at 160-MHz, and parylene substrate to provide the intraocular implant. Such complex systems are developed combining different Key Enabling Technologies (KETs) which are main contributors to overcoming the challenges involved in the development of an implantable device. Figure 2 introduces the suggested share of cross-cutting KETs involved in the development of a nano-enabled implantable device for _in vivo_ biomarkers monitoring. Current research is focused on the miniaturization and progression of the implants [45], in pursuit of less powering and long monitoring devices.