The Merging of Biological and Electronic Circuits

Abstract

Biological circuits and systems within even a single cell need to be represented by large-scale feedback networks of nonlinear, stochastic, stiff, asynchronous, nonmodular coupled differential equations governing complex molecular interactions. Thus, rational drug discovery and synthetic biological design is difficult. We suggest that a four-pronged interdisciplinary approach merging biology and electronics can help: (1) The mapping of biological circuits to electronic circuits via quantitatively exact schematics; (2) The use of existing electronic circuit software for hierarchical modeling, design, and analysis with such schematics; (3) The use of cytomorphic electronic hardware for rapid stochastic simulation of circuit schematics and associated parameter discovery to fit measured biological data; (4) The use of bio-electronic reporting circuits rather than bio-optical circuits for measurement. We suggest how these approaches can be combined to automate design, modeling, analysis, simulation, and quantitative fitting of measured data from a synthetic biological operational amplifier circuit in living microbial cells.

Electrogenic Bacteria Promise New Opportunities for Powering, Sensing, and Synthesizing

“…Considering current research trends, the future direction of electronics will have five obvious features: a) ubiquity, b) flexibility and stretchability, c) component-free all-in-one systemization, d) biodegradability, and e) biointegration. [196][197][198][199][200][201][202] Electronic miniaturization will progress exponentially and trillions of electronic particles named "smart dust" will be sprinkled, monitoring everything on Earth. [203] Flexible and stretchable electronics will be easily integrated with a wide range of environments such as curvilinear and deformable surroundings and human body/organs.…”

“…[198,200] Stand-alone all-in-one electronics containing all functions but without distinct physical components will work similar to a living biological system that provides self-sustaining, self-assembling, self-repairing, and self-maintaining operational capabilities. [201,202] Electronics will biodegrade or physically disappear in a controlled manner without environmental issues caused by electronic wastes. [196,197,204] Finally, there will be a direct interface between electronics and living organisms, allowing the close proximity of massive signal processing with those of complicated biological systems.…”

“…[196,197,204] Finally, there will be a direct interface between electronics and living organisms, allowing the close proximity of massive signal processing with those of complicated biological systems. [200,201,205] While biological living systems use molecules and ions nonlinearly for their metabolic activities and signaling, electronics exclusively and deterministically depend on electrons. [205] Electrogenic bacteria have been considered as an excellent tool for effectively interfacing electronics with biology because their EET process can bridge the signal gap between these two realms.…”

Measuring and modeling energy and power consumption in living microbial cells with a synthetic ATP reporter

“…5: The model includes glucose consumption, bacterial growth, acetate production corresponding to overflow metabolism and its subsequent consumption, oxygen dynamics, total population ATP dynamics, and individual cellular ATP dynamics. The differential equations can be conveniently represented and visualized as electric circuits as well (Additional file 6: Figure S6), as reported in our previous publications [37][38][39][40][41][42][43]. Our circuit models were simulated in the Cadence Virtuoso Analog Design Environment (Cadence Design Systems, Inc.).…”

“…The capacitors (C), representing volume, are always normalized to 1 F to match the differential equations used to describe the time dynamics of concentrations. More detailed explanation is in the reference [43]. Additional file 8: Table S1.…”