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Thanks for the question! In contrast to their synthetic counterparts, biological nano- or microrobots can sense and respond to changes in their local environment, providing a higher level of autonomy. Also, most microorganisms can achieve high propulsion speeds (tens of their body lengths per second) and interact with their targets at the same size scale (1–10 μm). Such advantages make biohybrid cellular microrobots attractive candidates for medical applications, including targeted drug delivery. These are the main advantages, however, this is not to say biohybrid microrobots are always superior to synthetic ones since the selection of the micro and nanobots is highly application dependent.

All the best,
/birgül

There are many technical challenges. All the synthetics parts that you want to equip your bacteria with should add an extra function to your swimmer. For instance, in our case, magnetic nanoparticles are added for swimming control using external magnetic fields, and nanoliposomes loaded with drugs are added for the demonstration of on-demand, localized drug release. One needs to carefully choose these synthetic components for the desired application, and design them accordingly. They need to be compatible, non-toxic, ideally smaller than your microorganism, and fully functional. Also, your microorganism should be able to accommodate the attachment of these synthetic cargoes. We use something called “biotin-avidin” interaction to equip bacteria with the components, and this had previously required the genetic modification of bacteria to express “biotin” on their cell surfaces, which is not a simple task either. Microorganisms also shouldn’t stop swimming after the addition of the synthetic components, because we want to harness their motility for active therapeutic applications.

Overall, designing a tiny robot out of a living, motile microorganism requires extensive planning and design on material development, genetic engineering, microscopic imaging, and viability checks after modifications and testing of their functions after the construction is complete.

Thanks for your question!
All the best,
/birgül

Is this making them swim i directions you choose or is it more like dragging them about?

Does the magnetic tool(s) that control them have to be super close, like contact with the body?

Hi! Oh, I would love that, that could make life MUCH easier if bacteria could listen to the voice of reason! But no, we do it pretty scientifically!

In our work, the synthetic components were integrated onto Escherichia coli. We use a strain of E. coli that allows for one-step binding of such nanoparticles through a physical complex known as “biotin-streptavidin complex”. Basically, these bacteria have “biotin” protein that binds to the “streptavidin” protein that is on the surface of the nanomaterials we use here. We mix them together under certain conditions (temperature, shaking, and the type of liquid media are all very important), et voilà, your bacterial biohybrid microswimmers are ready.

Thanks for the Q.
All the best,
/birgül

Thanks for your question! We attach nanomagnets on E. coli and control them using bigger magnets (centimeter scale) or electromagnetic coils for precise steering. Magnetized bacteria still swim using their flagellar propulsion, but follow the magnetic field lines, therefore making it possible for us to control them externally using magnetic fields.

All the best,
/birgül

These are very interesting questions! Let me try to answer as much as I can.

As I mentioned in a previous question about “how close we are to using these medical tiny robots in clinics”, currently this technology is not there yet. There are many, many promising studies with animal models, for example, showing the localization of microrobots on tumor tissues for targeted drug release. Nevertheless, we still need extensive research on other aspects including safety, imaging, tracking, and controlling of these robots. Therefore, I cannot exactly give you numbers, since they are currently not commercialized.

As for the second question, the biggest concern would be safety. If the material(s) used in the robotic design is immunogenic, there is already the risk of an immune reaction. This could not only eliminate your tiny robot before it can do its job but also generate a health risk. Additionally, let’s say you plan to administer your robot through the circulatory system, then the size and shape of the robot are crucial since you wouldn’t want the clogging of the vasculature.

And for the last question, I haven’t played the game or seen the show (yet), but I am currently reading a book on fungi (it’s called Entangled Life: How fungi make our worlds, change our minds and shape our futures, by Merlin Sheldrake, it’s a super cool book, 100% recommend) and just recently found out about Ophiocordyceps unilateralis, aka zombie ant fungi. The mechanism of taking control over an ant compared to a human is drastically different. Turning people into “zombies” is rather sci-fi than science, but many organisms (viruses, bacteria, fungi, parasites, etc.) do have an enormous impact on human life that we cannot disregard.

All the best,

/birgül

Super interesting work. I happen to work in related field. What is the advantage of using bacteria as drug carriers compared to nonliving systems? For example, similar targeting approaches have been explored using superparamagnetic iron oxide. Is there a concern that chemotherapeutic could be metabolized by the bacteria? Thanks!

Thank you for your questions. Here in our study, what happens is that we attach nano-sized magnetic particles to bacteria, and therefore, we are able to control those bacteria using external magnetic fields. You can imagine a single bacterium turning into a tiny magnet that can be navigated using a larger magnet, or electromagnetic setup. As for the colonies, with our optimized method, we were able to generate millions of these bacteria (we call them bacterial biohybrids), carrying the magnetic nanoparticles, meaning that we were able to control the swarms of bacterial biohybrids using external magnetic stimuli. Magnetic control mechanisms are quite robust since magnetic fields are safe to use in clinics and it allows for precise control over tiny swimmers. We can technically “steer” them using our electromagnetic coils, they go right when you press right, and go up when you press up on the control panel!

Hope this answers your questions!
All the best,

/birgül

Hi! I am no expert on genetics since I am trained as a Chemical Engineer, I may not be able to answer your question fully. As far as I know, genetic drift cannot be stopped from occurring since it is an event based on random chance. In bacteria, we can rather talk about mutations, which would happen over a long period. In our case, the envisioned therapy is very short term: injection, therapy, and removal. Therefore, current projections do not give us any reason to be concerned about the possibility of bacterial genetic drift or mutation.

All the best,
/birgül

Thank you for your question!

To be able to reach that point, where we can safely administer medical micro- and nanorobots to human bodies to carry out various medical tasks, some challenges remain to be tackled.

Firstly, the micro- or nanorobot should be safe for injection – meaning it should be biocompatible for its application, and should still be actively controllable to target specific regions. This requires extensive research on material development, safety tests, and wireless control mechanisms (such as magnetic fields, light, acoustics, etc.). Currently, hundreds of different medical micro and nanorobots are tested on Petri dishes and animal models, and many promising candidates could perhaps one day turn into clinical success.

However, that is not the end of it. Once your tiny robot is good to go, then we need real-time medical imaging techniques to be able to precisely detect and visualize these robots inside the body. Currently, many imaging systems are developed to increase the resolution and overcome the imaging limits such as our tissue penetration depth. Another important aspect that is commonly overlooked is the removal or elimination of the biohybrid microrobots after the treatment. Approaches regarding retrieval of the microrobots should be investigated as well. Additionally, active control mechanisms should be scaled up for human use, since currently reported setups are mostly designed for proof-of-the-concept studies and small animals.

We need many more in vivo and then pre-clinical studies that rigorously investigate the feasibility of these tiny robots. Therefore this is currently not a “ready-to-use” technology that our society can benefit from when it comes to treating patients, however, it holds great promise, and considering the exponential increase in the research of nano- and microrobots to overcome mentioned challenges, it is not far-fetched to imagine the use of medical robots in clinics in the future.

All the best,
/birgül

Hello everyone! Birgül here.

First of all, thanks for all the amazing, interesting, and stimulating questions! I am now online and will try answering as many questions as I can within the next hour!

In the meantime you can check our recent work on bacterial biohybrid microrobots here: https://www.science.org/doi/full/10.1126/sciadv.abo6163

Also, here is my Twitter: https://twitter.com/akolpoglu

All the best,

/birgül

In what ways (if any) could this type of technology hypothetically be abused or used with ill-intent? Would it be possible in the future for someone to weaponize this type of technology? How would this be counteracted?

Could they be used to take control of a brain?

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Wasn't the 'dust is mostly dead skin cells' idea debunked?

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Hello! It's so awesome to meet you! Thanks so much for the breakthrough that you are working on! It's amazing!

One question! How do you encapsulate the chemical transported inside the bacteriabot to avoid interacting or being metabolized by the bacteriabot itself until it gets to it's destiny?

Ok, I didn't know where you were going with "As long you have liquids" but think I get it now.

You make a good point about the radiated energy of the sun only being converted to heat once it strikes matter. Orbiting high energy reflectors could make a planet habitable closer to a sun. On distant planets, low altitude energy absorbers which reradiate IR could raise surface temps enough to boost biology which conditions the atmosphere favorably.

It wouldn't make much difference on a cosmological scale, but to an intelligent species facing extinction, it might be something they/we would attempt at the edges of goldilocks zones to eek out a few more generations.

Is there any crossover in your studies with The Last of Us fungal pandemic scenario? Could your studies produce a defence to it?

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Just a clarification, woody plants can include both monocots and dicots. Woody-ness (a shrub or treelike form) is a trait that has evolved many times independently in plants. Monocots and dicots refer to the number of seed leaves these clades possess (one and two respectively), amongst other differences.

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That is a common definition, yes, but scientifically liquid is a state of matter. Fluid =/= liquid. Liquid is a phase, fluid is behaviour. You said liquid when you described fluid and while that is correct in common meaning it's unnecessarily confusing people when the difference is described.

https://www.thoughtco.com/definition-of-liquid-604558

https://www.thoughtco.com/definition-of-fluid-604466