cell-electronic hybrids
Interfacing cells with electronics to build a new class of devices.
A couple of months ago, I wrote about a paper that discussed the search for synthetic biology’s “killer application”: a task that engineered cells, and only engineered cells would be best suited for.
One of the big promises of synthetic biology is that cells can be engineered to sense, process, and actuate, like robots. When we are working with a natural system, like a body of water in which we want to detect pollutants, or soil in which we want to selectively fixate nitrogen and other nutrients, genetically engineered cells are uniquely equipped to interact with the system, sensing low chemical concentrations or producing and releasing biomolecules. In such cases, using cells as sensors and actuators that are connected to electronic devices allows us to read from and control them in real time, and in potentially complex ways.
As it turns out, many microorganisms respond to, exhibit, or are modified by electrical signals (a property known as electroactivity). One of the most well-known examples of this is neurons, which communicate electrical signals throughout the nervous system to control our muscles. The two model organisms for electromicrobiology are the bacteria Geobacter sulfurreducens and Shewanella oneidensis.
Synthetic biologists have drawn on electromicrobiology to program cells as (1) sensors that transduce biochemical signals (chemical concentrations, push/pull forces on the cell, etc.) into electrical signals, as well as (2) actuators that are triggered by electrical signals to act in various ways. By connecting these synthetic electroactive cells to electronics, we end up with hybrid devices that we can use to monitor and control biological environments.
One of the most exciting things about biological electronic devices is that we can take advantage of microbes’ ability to self-assemble, self-repair, and self-power. (The disadvantage is that they do not do this task perfectly, which could lead to undesired consequences—see my thesis!)
One application of such a device is in DNA data storage (see my earlier post). DNA is a stable, energy-efficient, and highly dense way for cells to store information—1000 times more dense than our most compact solid-state drives. It is, at first glance, an attractive way for us to store digital information, but the time and cost of artificially synthesizing DNA molecules is too high to justify it. In this paper, researchers build an electroactive CRISPR system, enabling them to write data into DNA by delivering electrical signals to an engineered cell, directing it to synthesize DNA. (There isn’t yet a way to read this data out from cells—having this would enable us to build larger data storage/retrieval systems.)
fabricating biological electronics
A number of techniques already exist that allow us to pattern cells onto electrodes. Optogenetic, or light-based, control can be used to express specific proteins that cause a cell to adhere to the surface of an electrode. Another approach is first patterning the electrode with single-stranded DNA, then engineering cells to display the complementary DNA strand on their surface, causing the cells to bind to the electrode only where there is DNA. A final approach is patterning the electrode with conductive material, then applying a voltage, which attracts electroactive cells to the parts of the electrode covered with the conductive material.
thoughts
This was my first time reading about these cell-hybrid devices;1 they made a more compelling case for using synthetic biology than standalone cellular computers do. By pairing up electronic and biological systems in this way, we can take advantage of the strengths of both cells (unique sensing and actuation abilities, transduction abilities) and electronic devices (faster processing, more complex logic, ability to connect to larger programs). For the standalone cellular computing enthusiasts, this could also just be seen as a more palatable step towards cellular computers, because it piggybacks on existing computing technology (which we understand well).
I also think these kinds of devices could be commercialized fairly easily, at least compared to therapeutics. In general, non-therapeutic applications of synthetic biology are probably easier to get through government regulations because they don’t involve human testing (and the onerous associated regulatory pipeline).
Find the paper here: Atkinson, J. T., Chavez, M. S., Niman, C. M., & El‐Naggar, M. Y. (2023). Living electronics: A catalogue of engineered living electronic components. Microbial Biotechnology, 16(3), 507–533. https://doi.org/10.1111/1751-7915.14171
Another related (and somewhat controversial) area of research is wetware computing, which interfaces organoids, or small clusters of cells (usually neurons) with electronics, using the organoids as to process information.