A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.

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Figure 1. Analogies between (a) molecular flux in chemical reactions and (b) electronic current flow in subthreshold transistors. The mean current flow and stochastics of Poisson flow are similar in both domains [1].Figure 2. A simplified overview of the processes of induction, transcription, and translation in a bacterial genetic circuit.Abstract-We show that compact analog current-mode circuits are effective at quantitatively modeling the behavior of genetic circuits. We present experimental biological data from genetic activator (PBAD) and repressor (PlacO) promoter circuits in E. coli. Simple subthreshold cascaded-differential-pair transistor circuits have input-output characteristics that quantitatively represent this data. Such foundational analog circuits can provide efficient conceptual, modeling, and simulation tools for the design and analysis of circuits in synthetic and systems biology.

Charge pumping measurements were performed to characterize the interface between silicon and bottom oxide in silicon–oxide-nitride–oxide–silicon memory transistors, where information is stored as charges in nitride at the edges of the channel. The charge pumping signal was found to strongly increase with the number of performed program∕erase cycles, thus indicating the creation of traps with a density on the order of 1012cm−2 (after 100 000 cycles). To estimate the length of the degraded region, the charge pumping signal dependence on the drain voltage was compared with the simulated drain depletion length using TSUPREM∕Medici software. The damaged length calculated from the metallurgical junction is about 200Å at the beginning of the endurance test and increases to 500Å after 100 000 cycles.