title: A 1.26 μW Cytomimetic IC Emulating Complex Nonlinear Mammalian Cell Cycle Dynamics: Synthesis, Simulation and Proof-of-Concept Measured Results.
abstract: Cytomimetic circuits represent a novel, ultra low-power, continuous-time, continuous-value class of circuits, capable of mapping on silicon cellular and molecular dynamics modelled by means of nonlinear ordinary differential equations (ODEs). Such monolithic circuits are in principle able to emulate on chip, single or multiple cell operations in a highly parallel fashion. Cytomimetic topologies can be synthesized by adopting the Nonlinear Bernoulli Cell Formalism (NBCF), a mathematical framework that exploits the striking similarities between the equations describing weakly-inverted Metal-Oxide Semiconductor (MOS) devices and coupled nonlinear ODEs, typically appearing in models of naturally encountered biochemical systems. The NBCF maps biological state variables onto strictly positive subthreshold MOS circuit currents. This paper presents the synthesis, the simulation and proof-of-concept chip results corresponding to the emulation of a complex cellular network mechanism, the skeleton model for the network of Cyclin-dependent Kinases (CdKs) driving the mammalian cell cycle. This five variable nonlinear biological model, when appropriate model parameter values are assigned, can exhibit multiple oscillatory behaviors, varying from simple periodic oscillations, to complex oscillations such as quasi-periodicity and chaos. The validity of our approach is verified by simulated results with realistic process parameters from the commercially available AMS 0.35 μm technology and by chip measurements. The fabricated chip occupies an area of 2.27 mm2 and consumes a power of 1.26 μW from a power supply of 3 V. The presented cytomimetic topology follows closely the behavior of its biological counterpart, exhibiting similar time-dependent solutions of the Cdk complexes, the transcription factors and the proteins.
authors: Alexandros
authors: A
authors: Houssein
authors: Konstantinos I
authors: KI
authors: Papadimitriou
authors: Emmanuel M
authors: EM
authors: Drakakis
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D012666:Semiconductors
chemical_list: D018844:Cyclin-Dependent Kinases