The Importance and Usage of Escherichia coli on the Internet of Bio-Nano Things ~ A Literature Review by Mridini Manivannan

The Importance and Usage of Escherichia coli on the Internet of Bio-Nano Things 

- Mridini Manivannan

What is the Internet of Things?

From the first telegraph lines and radio transmission to smart ovens and modern precision
medicine treatments, the last few decades have seen steep rises in technological advancements and its’ widespread usage and importance across various fields. This has raised the necessity of connecting devices to more connected devices, the internet, and people, to gather and share data, about the way devices are used and their surroundings. This is the Internet of Things. This giant network has now become part of our every-day lives; so long as the connected devices have embedded computing abilities.

Applications opened by IoT and connectivity:

Connectivity opens a lot of new possibilities and allows us to venture forth and create new, improved technologies to increase accessibility, automate processes, improve efficiency of old technologies and to optimize the tasks they perform.

Some of these applications are, machine to machine communication, real-time monitoring of industrial processes, smart grids for energy management, medical and healthcare systems and monitors and building and manufacturing automation and deployment. These are widely available in most places and are being further developed still.

Further development on IoT:

Certain IoT devices required unnoticeable and non-invasive ‘things’ to function. This has inspired the Internet of Nano Things, which uses nanomaterials, like graphene, to connect nanoscale devices. It has been found however, due to recent study and development, that these ‘nano-things’ can be causes of undesirable health issues and pollution because of their artificial nature – therefore have the disadvantage of being unsafe for use inside the human body – and electro-magnetic radiation emitted by these devices.

To prevent the above stated effects of IoNT, a new sub-field, called the Internet of Bio-Nano Things is being researched and developed, to be predominantly used inside living organisms.

About the Internet of Bio-Nano Things:

Biological cells are the basic units of life. They have many specialized molecules and organ-like structures enclosed by a membrane. They, therefore, have the capability to act like an IoT embedded computing device, with internal components and circuits.

IoBNT is an up-and-coming sub-field of IoT. As the name suggests, it is an interface which combines the Internet of Things with nano-scale biological organisms, bacteria, and other synthetic organisms. These organisms are improved to interact and work with real-world communication channels, such as, the internet.

IoBNT enables safe exchange of data between the bacteria and human interface. Interactions between and within the bio-chemical and electrical domain of the internet can take place.

Bacteria are widely used in IoBNT, as they can communicate efficiently and have built-in receptors and devices. These micro-organisms also have circular structures called Plasmids which carry genetic information as genes, instead of a nuclear envelope. This shape allows for more gene sequences to be added, or some removed. These are easily accessed by biotechnologists and can hence, be easily modified and inserted back into the bacterium, and it will have to keep the recombinant plasmid. Exact copies of these bio-engineered organisms are made as their population multiplies, which can then be harvested for use.

Applications opened by IoBNT:

Over the last decade, scientists have been implementing IoBNT in the field of medicine, and

although, a relatively new aspect, IoBNT is proving to be invaluable in medical treatments and has also allowed for developments in biotechnology, like genetic engineering.

These are enabled by transformation of chemical energy, and exchange of information through transmission and reception of molecules, the biochemical processing of data and DNA based instructions.

Intra-body sensing: Bio-nano things in the body collectively gather health-related information; such as the constituents of its’ surroundings and transmit it to a device connected to the internet. They can then carry out operations from commands like synthesis and releasing drugs. An example of this use is in immunotherapy, as a treatment against cancer. The re-programmed E.coli bacteria can particularly grow inside cancerous tumours and can release drugs . They can multiply in the tumour (which provides ideal

conditions for E.coli to thrive) and with the use of biological circuits and sensors, can be programmed to release the drugs on a set schedule, based on how long a population survives.

Intra-body connectivity control: E.coli would repair or prevent communication failure between internal organs of an organ system, and hence prevent many diseases, especially related to the nervous system and endocrine system. As these are effectively, engineered computing devices, they may be reliable while administering medication, to prevent overdoses or underdoses. Bacteria can constantly monitor intra-body conditions and levels of toxicities, thereby preventing harm to healthy body cells.

Environmental control and cleaning: When released into the environment, bio-nano things

can check for toxic wastes and other pollutant agents, then collectively transform them by

bioremediation. This has been popularly used while cleaning large oil spills.

Smart agriculture: As a specialized development on environmental control and cleaning,

IoBNT can be used to monitor health and growth of cattle and plants in agriculture. They

can also be designed to control these.

What is inside a Bio-Nano Thing?

Bio-nano things are defined as uniquely identifiable basic structural and functional units that

operate and interact within the biological environment and are required to carry out operations distinctive of the embedded computing device.

As bacterium cells are made of biological molecules and function due to biochemical reactions, the cells can be efficiently utilized by controlling, re-using, and reengineering its’ functionalities, like sensing, actuation, processing, and communication.

Various components in a biological cell can be compared in their similarity to the structural and functional components in an IoT computing device. The control unit, in the processor of an IoT device contains embedded software of the device and is in similarity to densely packed DNA molecules in a bacterial cell and plasmids. It contains sequences of proteins which act as regulatory sequences for the cell. The memory unit of the IoT device, which holds values of the system data, corresponds with cytoplasmic fluid and components in a bacterial cell, containing molecules synthesized by cells because of DNA instructions. The processing unit in an IoT device, which carries out software instructions and manages memory and peripherals, can be compared to the process of Transcription-Translation for protein synthesis, which results in formation of DNA molecules, and are instruction-dependant. The power unit, which supplies energy to retain electrical circuits in the IoT device, resembles the biological molecule ATP (Adenosine Tri-Phosphate) in biological cells. These are synthesized from energy supplied to the cell and provides energy required for other biochemical reactions to take place. The transceivers in IoT devices which allow an exchange of information between connected devices, correspond to specific chains of chemical reactions in a cell. These are signalling ‘pathways’ for transmission of information-carrying molecules. Sensing and actuation, functions of an IoT device, which allow it to acquire data and interact with the environment, are also present in bacterial cells in the form of receptors. These can sense light, temperature, and other conditions in its biological environment, and so, the cell can interact with it.

For communication to happen between the embedded computing device and the bio-

hacked bacterial cell, a bio-cyber interface is used. This is essentially a specialized micro-

device, which is implanted on the outer parts of the body. This translates biochemical signals from the cell, into electrical signals sent to heath care providers and vice versa. This is a wireless communication capability, and the communication frequency is kept low, so as not to interfere with other bodily functions.

Why E.coli?

Escherichia coli, are rod shaped bacteria, that are found in thriving populations in the lower intestines of warm-blooded organisms, including humans. Unlike most bacteria, a lot of the E.coli strains are harmless; an important factor when considering usage in precision medicine related treatments, which require the bacteria to be injected into a patient.

Sensors in their peptidoglycan cell walls can sense temperature, light, and chemicals, permitting them to subsist in and access the environment, which other human-made technologies have difficulty accessing. They are – in comparison to other species – easy to engineer, and are resilient, cost-efficient, and are effective in moving data around the world.

These highly specialised, miniature sensors could predict closeness, environmental factors, and site information to help ensure the safety and accuracy of communication systems and other connected interfaces. Said data is collected and passed to the bio-cyber interface for interpretation, or inside the human body for biomedical purposes.

The most used lab strains of E.coli used are B and K-12 strains, as they are the most harmless ones. These are also the strains which are very efficient at transmitting and processing information. Other lab produced strains which are derived from B and K-12 are also used, keeping in mind the motility of the bacterium, the extent of cloning required and rate of growth of the bacterium.

Conditions required to grow E.coli:

• Warmth: 37.4 ̊C, body temperature. Easy to maintain and work with for scientists.
• Nutrition: found in their natural environment (the gut), digested foodstuff.
• Oxygen: (optional - They can respire with or without oxygen.)

Other reasons why E.coli are useful:

• Used in cloning, as exact copies are made, DNA of other species and E.coli are compatible, genes can be transferred i.e., Cut and Pasted.
• E.coli genome has been fully decoded, genome has been published and studied extensively.
• Function of proteins can be predicted, therefore. By studying the genome, 4400 genes which are known precisely.
• Grows/multiplies fast and population doubles around every 20 minutes. Faster than almost all other species of bacteria.
• Inexpensive, in fact, cheap, and extremely easy to store. Cultures can be stored at low temperatures for years.
• The medium for E.coli is also cheapy and easily made.

Difficulties and problems faced:

• Since IoBNT devices and Bio-Nano devices are required to interact via transfer of signals, such as synchronisation, logical operations and other physical and chemical sensing, knowledge must be gained as to how these natural signals can be reengineered, organized, and controlled for transmission of information to happen. These must also be suitable for the environment the Devices are to be used in. Tools for the above-mentioned processes are currently in development and are distance specific as well (very short range, short range, medium range, and long range).

• Bio-Nano networks can be difficult to achieve because molecular information does not go by the predicted paths and definite propagation directions as in typical IoT networks (electromagnetic). The diffusion of bacterial molecules and filaments supporting their molecular motors have a tendency to overlap and follow random patterns between their starting point and destination. Another irregularity is the non-linear nature of most biochemical phenomena, render it quite hard to make use of classical regulatory methods in Bio-Nano things. Important basic aspects of computer networks, such as access to shared media and designing data steering devices must be developed on and altered to behave accordingly, in Bio-Nano devices.

• Actualizing bio-cyber interfaces can be a challenge, where chemical and physical processes are to be reengineered to correctly read the molecule traits where data is encoded. This must then be translated into adjusting electromagnetic factors, to be processed by other connected computing devices. (also called biocompatibility)

• Bio-cyber terrorism could arise, posing a severe security threat. This could take advantage of the numerous applications opened by IoBNT to manipulate and interact with the biological environment. They can be used to illegally access the human body and steal health-related information or even cause new diseases. Some viruses can be employed to hack into IoBNT devices and alter their functioning. Security checking measures used in typical computing devices must be introduced and integrated into IoBNT to create a more secure bio-nano network.

• IoBNT devices must actualize tracking, in the form of wireless senor networks to transmit or receive information or commands, such as directions, location, medicine dosage, environment conditions etc. This could involve the engineering of bacterial molecule diffusion(chemotaxis), based on the ability of bacteria to locate, and track their sources, via ‘bio-markers’.

• A rarer challenge which could be faced, is the mutation of the bacterial cells. As biological entities, they are prone to changes in their genes as they are copied, and this can sometimes result in disadvantageous capabilities, which may cause their death or malfunctioning in their biological environment. They will therefore be dangerous to use inside the human body, as an incorrect dose of medicine or inaccurate monitoring of conditions inside the body can put the persons’ life at risk.

• One other challenge to be managed would be the management, storage, and utilization of a large amount of data collected and sent in the bio-nano network. Types of data sent to IoNT and IoBNT devices also needs to be mapped and new discoveries must be made to explore in depth, the biological environment and interaction between other bio-nano devices and connected computing devices to collect or utilize information.

Conclusion:

Advancements being made in the field of the Internet of Things, can lead us to believe that if and when these advancements are utilised in making bio-nano things, they can be used in the most efficient manner possible. We may potentially be able to treat diseases that we previously could not, detect diseases at an early stage and provide medication on time, monitor intra-body conditions accurately and detect even the smallest hindrances before they become a problem. Furthermore, the development of the Internet of Bio-Nano Things will ensure that more technological advances are being made, bringing humanity closer to understanding biological phenomena around us, giving us the ability to protect ourselves and others from the suffering caused by deadly diseases and highly efficient ways of doing so, will also be known and available to us. 

References:

1. RT insights – Raphael Kim and Stefan Poslad (Queen Mary University of London);
2. www.ibm.com/blogs/internet-of-things/what-is-the-iot/; https://internetofthingsagenda.techtarget.com/answer/What-is-the-internet-of-nano-things-and-what-are-its-uses; 
3. https://www.hackernoon.com/wtf-is-internet-of-bio-nano-thingsiobnt-and-how-secure-is-it-v62z32a5; www.arm.com what-are-smart-devices?;
4. www.digitutes.com ; E. coli - the biotech bacterium - Science Learning Hub; 
5. What Is the Internet of Bio-Nano Things? - IoT Tech Trends; Bacterial DNA - the role of plasmids Science Learning Hub;
6. IEEE Communications Magazine — Communications Standards Supplement • March 2015 THE INTERNET OF BIO-NANOTHINGS, I. F. Akyildiz, M. Pierobon, S. Balasubramaniam, and Y. Koucheryavy ; 
7. The thing with E.coli: highlighting opportunities and challenges of integrating bacteria in IoT and HCI – Raphael Kim and Stefan Poslad (Queen Mary University); 
8. The ITU Journal on Future and Evolving Technologies;
9. lifeandbiology.com/2018/05/25/why-work-with-escherichia-coli-e-coli/;

Image Credits :

Fig 1 – Iottechtrends

Fig 2 - IEEE Communications Magazine — Communications Standards Supplement • March

2015 THE INTERNET OF BIO-NANOTHINGS, I. F. Akyildiz, M. Pierobon, S. Balasubramaniam,

and Y. Koucheryavy

Fig 3 - E. coli - the biotech bacterium - Science Learning Hub

Fig 4 - The thing with E.coli: highlighting opportunities and challenges of integrating bacteria

in IoT and HCI – Raphael Kim and Stefan Poslad

Fig 5 – Tampere University of Technology

Fig 6 – IEEE Xplore

My Research summary on E.coli and the Internet of Bio-Nano Things. Please note that this is not meant to be reproduced or distributed in any way. I would really appreciate you reaching out to me in the comment section before using any content directly from here. Thank you.  ~ April 2021