New Therapeutic Devices for Diseases with ‘Internet of Life’

Although an electronic gadget and E. coli bacteria might not seem to have much in common, University of Maryland researchers recently connected them to create the first closed-loop system capable of communication across the technological and biological divide.

In a recent paper published in Nature Communications, a team from the Robert E. Fischell Institute for Biomedical Devices and the Institute of Bioscience and Biotechnology Research (IBBR) demonstrated how chemical reactions and genetic engineering can be used to control biological processes of cells in real time using electronic signals.

The study is being done by Bioengineering Professor and Fischell Institute Director William E. Bentley along with, IBBR Research Professor and Fischell Institute Fellow Gregory F. Payne.

The first step towards creating translatable “smart” healthcare devices like medication delivery systems for diabetics or real-time disease progression trackers for cancer patients. (E. Coli is a commonly used microorganism in experiments due to its ease of propagation.)

For years, the two researchers have collaborated to progress bioelectronics. They claim that although there have been significant advancements in bioelectronics with devices like electrocardiograms and defibrillators that use electrical signals from the heart, there is still a need for low-tech devices that can access molecular information for health metrics and disease treatment. Their recent progress may start to fill this need.

A longstanding impediment to commercialized bioelectronics technology is the ability to successfully establish a seamless connection between biological systems and electronic devices, and as with so many complex relationships, the core of the solution requires good communication the successful exchange of information.”

William E. Bentley, Professor and Director, Fischell Department of Bioengineering, University of Maryland

In wireless communications, electromagnetic waves carry the data instead of electrons moving through wiring and circuitry as in conventional electronics.

In biology, there are not free electrons moving through your body, so what do biological systems do to move those electrons? They transfer electrons using redox reactions.”

Sally Wang, Study Co-Lead Author and Postdoctoral Researcher, University of Maryland

Cells produce redox (or reduction-oxidation) molecules, which use redox chemical reactions to move electrons from one location to another. This process results in the gain and loss of electrons within cells. Vital biological processes like photosynthesis and respiration depend on this electron transfer, which modifies the oxidation levels in cells.

Since proving that redox reactions can connect biological and electronic systems almost six years ago, Bentley and Payne have worked to design and control biological redox networks for the transfer of bioelectronic information at several levels, such as proteins, single cells, and clusters of cells. The team has dubbed this complex and intricate relationship between systems the “Internet of Life.”

Building on these findings, Wang and Chen presented a closed-loop system that allows for the electronic control of a cell's genetic systems in addition to real-time biological activity monitoring via electronic signals. This latter function is known as “electrogenetics,” a method that the UMD team pioneered and that has since been embraced by numerous organizations across the globe.

The scientists modified E. Coli bacterial cells to incorporate proteins and antibodies from other organisms, such as jellyfish and Pseudomonas bacteria, using the gene editing technique CRISPR.

This allowed the bacteria to react to electricity in a particular way: They emit fluorescence in response to electrons, which can be captured and processed in real time by a machine as optical signals. Subsequently, the device can determine if it requires additional current to maintain the electron transfer between systems, thereby exhibiting a cycle.

Through redox reactions, the engineered cells can accept electrons from both electrodes and other cells, effectively making them “bilingual.”

Bentley added, “This opens doors for building completely new ways to connect information and data-rich technologies to biology, and there are myriad opportunities that could emerge from electrogenetics.”

Apart from advancements in healthcare, such as an autonomous device that is linked to the body and can accurately monitor illnesses and administer medications, there are potential uses for this technology in environmental preservation and agriculture.

For instance, a “smart” farmland monitor could telemetrically offer guidance on when and how much to apply herbicide and pesticide to maximize the microorganism content of the soil.

Source:
Journal reference:

‌Wang, S., et al, (2023) Redox-enabled electronic interrogation and feedback control of hierarchical and networked biological systems. Nature Communications. doi.org/10.1038/s41467-023-44223-w

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