A Versatile CMOS Enhanced Adaptive Biosensing Platform for Label-free Single Molecule/Cell Detection

Genes, proteins and cells provide a wealth of information essential for the diagnosis and treatment of diseases. Resistive-pulse sensing using solid-state nanopores and polymeric micropores has emerged as a new biomolecule-sensing platform. The technique involves sensing the ionic current flowing through a pore in an insulating membrane separating two ionic reservoirs. The blockage of this ionic current provides information on the length of the biomolecule (e.g. DNA), and physical characteristics such as size, stiffness and shape, (in the case of a tumor cell), enabling label-free detection.;This transduction of the biomolecular property to an electronic signature will enable low-cost, high-throughput, accurate and easy-to-use biomolecule detection platform, paving the road to personalized medicine. The realization of such a detection platform will also aid in the early detection of diseases, which in cases such as cancer can greatly improve the survival rate. The deformability of Circulating Tumor Cells (CTC), for example, was identified as a novel biomarker and has been proven to be an effective predictor for cancer metastasis.;In this work, the existing approaches, challenge and limitation were discussed and investigated. A fully integrated biomolecule sensor platform with digitally assisted baseline cancellation was designed and implemented in a 0.6micrometer CMOS process. The design is capable of sensing particle size spanning from DNA (nanometer scale) to cell (micrometer scale). The high dynamic range low-noise front-end compresses the signal logarithmically and encodes the signal into single-bit stream with a delta-sigma modulator. The baseline information is then digitally extracted and processed using an FPGA. Our proposed design can tolerate a steady-state base- line current of 10 micro-ampere and has a usable bandwidth of 750kHz. Experimental results from a 5kbp DNA sensed using a 5nm silicon nitride pore and mice J774A.1 macrophage cells sensed using a single micropore in a polyethylene terephtahalate (PET) film confirm the versatility of the CMOS sensing platform.