A CMOS integrated circuit hosting an array of 80 sensors for DNA hybridization detection was designed. Each biosensor is made up of a FET device whose current is modulated by DNA electric charge. The chip incorporates integrated temperature detection for precise assay control and features programmable signal conditioning, amplification and A/D conversion. Successful pre-and post-layout simulations are provided.
IntroductionThe standard, commercial approach to DNA hybridization detection is based on the use of fluorescent, radio-scope and other labels and can be schematically summarized in the following procedure: (a) a probe of single-stranded known sequence of DNA is immobilized on a substrate, (b) the unknown sequence (target) is labeled with a specific tag and (c) when hybridization occurs, the target sequence binds to its complementary strand immobilized on the surface and (d) its presence can be optically detected [1]. The required instrumentation is bulky, costly and not portable [2].For this reason, a number of new approaches for direct, label-free detection of DNA hybridization have been proposed in the last decade. Among them, detection based on quartz crystals microbalances (QCM) [3], cantilever-based techniques [4] and several examples of electronic detection methods [5]- [9]. Direct electronic detection has several advantages with respect to other approaches: the detector is incorporated in the substrate, the output signal can be directly acquired and processed on a chip, automatic recognition is achievable in real-time and at low-cost. Moreover, electronic detection by means of standard CMOS (Complementary Metal Oxide Semiconductor) devices would pave the way to the realization of simple, portable, inexpensive detection platforms, exploiting the advanced technology of consumer electronics.In this paper we present a DNA-chip hosting 80 sensing sites, entirely realized in a standard, commercially available, CMOS process, which allows direct electronic read-out of the outputs. The implemented detection principle is based on the modulation of the threshold voltage of a MOS transistor, induced by the intrinsic electric charge of the DNA molecule.