2D printed multicellular devices performing digital and analogue computation

Sira Mogas-Díez,Eva Gonzalez-Flo,Javier Macía

doi:10.1038/s41467-021-21967-x

Sira Mogas-Díez, Eva Gonzalez-Flo + Show 1 more

Open Access

https://doi.org/10.1038/s41467-021-21967-x

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Abstract

Much effort has been expended on building cellular computational devices for different applications. Despite the significant advances, there are still several addressable restraints to achieve the necessary technological transference. These improvements will ease the development of end-user applications working out of the lab. In this study, we propose a methodology for the construction of printable cellular devices, digital or analogue, for different purposes. These printable devices are designed to work in a 2D surface, in which the circuit information is encoded in the concentration of a biological signal, the so-called carrying signal. This signal diffuses through the 2D surface and thereby interacts with different device components. These components are distributed in a specific spatial arrangement and perform the computation by modulating the level of the carrying signal in response to external inputs, determining the final output. For experimental validation, 2D cellular circuits are printed on a paper surface by using a set of cellular inks. As a proof-of-principle, we have printed and analysed both digital and analogue circuits using the same set of cellular inks but with different spatial topologies. The proposed methodology can open the door to a feasible and reliable industrial production of cellular circuits for multiple applications.

Highlights

To date, most cellular computational devices have been designed according to a standard architecture that organizes their components into three different layers: the input layer, where external signals are detected; the processing layer, where computation is performed; and the output layer, where the final output is produced[1,2,3,4]
Two main issues needed to be addressed for the development of 2D printed circuits: (i) the optimal circuit architecture and (ii) the methodology for fast and reliable printing
Considering that computation is, in essence, a matter of information processing[32], our approach encodes the information in the concentration of a unique biological signal, the carrying signal (CS)[33,34]

Summary

Results

To take full advantage of our approach, we developed a set of cellular inks composed of a single cell type mixed with cellular nutrients and agar (used as a thickener) These inks were used to draw the different circuits in the paper (see Supplementary Information for details regarding the cellular inks and paper used). In order to prove potential applications of paper-based cellular devices, we created a very simple paper-based biosensor prototype responding to mercury This device is based on the minimal architecture shown in Supplementary Fig. 5a, composed by a CS supply cell (S4) that secretes AHL in the presence of mercury combined with a reporter cell CR expressing GFP in response to AHL (see Supplementary Fig. 1 and Supplementary Table 2 for details about the genetic architecture of the involved cells).

Discussion

Methods

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