Interfacing gene circuits with microelectronics through engineered population dynamics

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Science Advances  22 May 2020:
Vol. 6, no. 21, eaaz8344
DOI: 10.1126/sciadv.aaz8344
  • Fig. 1 Interfacing genetic circuits with electrical measurement.

    (A) Schematic of the approach using a culture of bacteria with a killing gene as the circuit output in contact with inert gold electrodes. The impedance of the culture reduces during growth (left) and increases upon the induction of bacterial death due to the clearance of charged metabolites (right). (B) Profile of the admittance (red), which is the inverse of impedance, using an IPTG-inducible lysis construct (pE35GFP) (42) in an electrochemostat device. The pink shaded region represents induction of lysis with 1 mM IPTG in the medium. (C) Schematic of the equivalent electrical circuit for our strategy using an alternating input voltage. The bacterial population is simplified to a resistor, which is controlled by a genetic circuit. (D) Schematic showing a microelectronic platform to interface between engineered bacteria and electronics. Several chambers may contain unique genetic circuits, connected via electrodes to an impedance output system.

  • Fig. 2 Interfacing bacterial circuits for impedimetric sensing.

    (A) Schematic and picture of electrochemostat components included in a 3D-printed holder containing a culture tube, in which the disposable electrode consisting of gold counter/reference (C/RE) and working (WE) electrodes are immersed, and an external turbidimeter detector. (B) Equivalent electrical circuit for a bacterial population engineered with an inducible promoter driving the expression of the lysis gene, E, and schematic of engineered bacterial (As-lysis) death upon arsenic induction. (C) Profiles of the admittance (red) and turbidity (blue) using an arsenic-sensitive strain in an electrochemostat device. The shaded region represents the duration of 250-ppb arsenic induction. (D) Profiles for the As-lysis strain induced with 250-ppb copper. a.u., arbitrary units. (E) Square-wave voltammetry profiles for 250-ppb arsenic (purple) and 250 ppb copper (orange). Dashed line shows the signal of the HNO3 buffer (background). The oxidation potential at the maximum current intensity versus background signal is indicative of the presence of the metal. (F) Heat maps of selectivity to arsenic versus copper using our bacterial lysis and chemical approaches. Photo credit: M. O. Din, UCSD.

  • Fig. 3 Interfacing genetic oscillators.

    (A) Schematic of the equivalent electrical circuit when using a SLC connected to the potential source. The circuit is composed of an AHL-based quorum sensing system driving a phage lysis gene (35). The protein LuxI regulates the synthesis of autoinducer, AHL, which binds to LuxR and activates lysis after a threshold population level. (B) Profiles of the admittance (red line) and turbidity (blue line) using this strain in an electrochemostat device. The SLC is harbored by a strain Salmonella enterica subsp. enterica serovar Typhimurium (see Materials and Methods).

  • Fig. 4 bICs in millifluidic devices.

    (A) Photograph of the bIC device (left) and schematic showing the design of the growth chamber and adjoining gold electrodes. Each bIC integrates lithography-fabricated electrodes, including a reference/counter electrode (R/CE) and a WE electrode, on 0.6-mm-diameter traps where bacteria form 3D continuous cultures. (B) Schematic of the equivalent electrical circuit illustrating multiple parallel interconnecting bICs measured with a single potentiostat. The dynamics in each bIC is measured sequentially in time intervals (Δt). A device containing n unique bICs may output an oscillatory signal at ti, a steady signal at tii, and other distinct signals up to tn. (C) Images of a bIC, containing the Salmonella SLC strain, were taken using transmitted light (TL). The bacteria begin at a low cell density (i) from which they reach the quorum threshold and lyse (ii and iii), and repeat the process (iv) cell growth in red is superimposed with the original time lapses in movie S1. (D) Profiles of admittance (red line) and inverse of the TL (blue line) for the strain in (C). (E) Images of the response of the bIC with the arsenic-inducible construct in E. coli MG1655 showing the steady growth state (i) and after 250-ppb arsenic induction (ii). (F) Profiles of admittance (red line) and inverse of the TL (blue line) for the strain in (E). Photo credit: A. Martin, UCSD.

Supplementary Materials

  • Supplementary Materials

    Interfacing gene circuits with microelectronics through engineered population dynamics

    M. Omar Din, Aida Martin, Ivan Razinkov, Nicholas Csicsery, Jeff Hasty

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