Researchers design a biological device capable of computing by printing cells on paper

The Synthetic Biology for Biomedical Applications research group at Pompeu Fabra University in Barcelona, Spain, has designed a cellular device capable of computing by printing cells on paper. For the first time, they have developed a living device that could be used outside the laboratory without the help of a specialist, and could be produced on an industrial scale at low cost. The study is published in Nature Communications and was conducted by Sira Mogas-Díez, Eva Gonzalez-Flo and Javier Macía.

We currently have at our disposal many electronic devices such as computers and tablets with very efficient computing power. But, despite their power, they are very limited devices to detect biological markers, such as those that indicate the presence of a disease. This is why, a few years ago, "biological computers" began to be developed, i.e. living cellular devices capable of detecting several markers and generating complex responses. In these devices, researchers exploit biological receptors that can detect exogenous signals and, by means of synthetic biology, modify them so that they emit a response according to the information they detect.

Until now, cellular devices have been developed that must work in the laboratory, for a limited time, under specific conditions, and must be manipulated by a specialist in molecular biology. Now, a team of researchers from Pompeu Fabra University has developed a new technology to "print" cellular devices on paper that can be used outside the laboratory.

Interestingly, they use an "ink" composed of different types of cells and nutrients to "draw" the circuits. The cells remain trapped in the paper, alive and functional, and there they continue to grow and are able to release signals that pass through the paper and reach other cells. The reason for doing this on paper (or other surfaces such as tissue) is mainly practical; it's cheap and easy to adapt for industrial use, and large quantities could be produced at very low cost. "We wanted to design a scalable model and we thought about using a printing system like the one used to print T-shirts," details Sira Mogas-Díez, first author of the study. "We make molds with our design, dip it with the different cellular inks like a stamp, put it on the paper and the cells are deposited," she adds. A highlight is that these paper-based devices can be stored in the refrigerator or even frozen, since the cellular ink incorporates cryoprotectants that allow this. So, unlike previous devices, they can be stored for long periods of time before being used.

In this new approach, each element of the device is a group of cells, in this case bacteria, with minimal genetic modifications that can sense different signals. The cells live in the paper strip and communicate with each other, integrate the signals and generate one response or another based on the different combinations of signals detected. The elements do not vary, but by changing their arrangement in space through the design they make on the paper, devices with different functionalities can be built. "Therefore, the order in which the cells are placed is the software, the cells are the hardware, and the paper is the physical substrate that hosts these cells," illustrates Javier Macía, coordinator of the work.

The research team has designed several biosensors, one of which has the specific application of detecting mercury. The contribution of the system compared to other existing systems is that it allows a visual estimation of the concentration of mercury without the need for a laboratory measurement device. Depending on the amount of mercury present, more or less numerous dots appear on the test strip and can be counted with the naked eye.

Another application under development is based on the detection of cholera in polluted water. "Localities where there is a risk of cholera often do not have a laboratory or specialist. So our idea was to develop a new method that would allow us to take live technology out of the lab and use it in the field. Our approach is attractive for tackling this type of problem because it is inexpensive and allows us to produce cellular devices in industrial quantities," Sira explains.

Another potential use would be to identify, for example, the risk of preeclampsia. Its detection does not depend on a single marker but on a complex combination of markers. A strip with the appropriately configured cellular device could detect combinations of biomarkers, analyze them and determine a pregnant woman's risk of developing the condition.

"There is certainly a lot of work to be done, but these initial results suggest that the methodology developed could be the way to facilitate the creation of commercial products based on living devices," concludes Javier Macía.



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