The field of nano-biosensors and nano-bioelectronics presents many opportunities as well as challenges. One of the challenges in nano-biosensors is its susceptibility to device and biomolecular artifacts which severely degrades its reliability. In this regard, a bio-silicon integration offers a unique opportunity for designing ultra-reliable biosensors where high degree of sensitivity and specificity offered by biomolecules (antibodies, aptamers, or enzymes) could be exploited in conjunction with high computational reliability offered by silicon circuits. At the core of this integration is a forward error correction (FEC) technique which exploits synthetic redundancy at the biomolecular level to correct for random and systematic errors. In this chapter, we first present the fundamentals behind FEC biosensors followed by an integrated nano-bio-VLSI design flow which is used for designing FEC biosensors. Each of the key concepts of this design flow is illustrated for a model immunoassay which uses antibodies labeled with conductive polyaniline nanowires for biomolecular encoding.