A miniature robot that could check colons for early signs of disease

Engineers have shown it is technically possible to guide a tiny robotic capsule inside the colon to take micro-ultrasound images.

 

Known as a Sonopill, the device could one day replace the need for patients to undergo an endoscopic examination, where a semi-rigid scope is passed into the bowel -- an invasive procedure that can be painful.

Micro-ultrasound images also have the advantage of being better able to identify some types of cell change associated with cancer.
The Sonopill is the culmination of a decade of research by an international consortium of engineers and scientists. The results of their feasibility study are published today (June 19th) in the journal Science Robotics.
The consortium has developed a technique called intelligent magnetic manipulation. Based on the principle that magnets can attract and repel one another, a series of magnets on a robotic arm that passes over the patient interacts with a magnet inside the capsule, gently manoeuvring it through the colon.
The magnetic forces used are harmless and can pass through human tissue, doing away with the need for a physical connection between the robotic arm and the capsule.
An artificial intelligence system (AI) ensures the smooth capsule can position itself correctly against the gut wall to get the best quality micro-ultrasound images. The feasibility study also showed should the capsule get dislodged, the AI system can navigate it back to the required location.
Professor Pietro Valdastri, who holds the Chair in Robotics and Autonomous Systems at the University of Leeds and was senior author of the paper, said: "The technology has the potential to change the way doctors conduct examinations of the gastrointestinal tract.
"Previous studies showed that micro-ultrasound was able to capture high-resolution images and visualise small lesions in the superficial layers of the gut, providing valuable information about the early signs of disease.
"With this study, we show that intelligent magnetic manipulation is an effective technique to guide a micro-ultrasound capsule to perform targeted imaging deep inside the human body.
"The platform is able to localise the position of the Sonopill at any time and adjust the external driving magnet to perform a diagnostic scan while maintaining a high quality ultrasound signal. This discovery has the potential to enable painless diagnosis via a micro-ultrasound pill in the entire gastrointestinal tract."
Sandy Cochran, Professor of Ultrasound Materials and Systems at the University of Glasgow and lead researcher, said: "We're really excited by the results of this feasibility study. With an increasing demand for endoscopies, it is more important than ever to be able to deliver a precise, targeted, and cost-effective treatment that is comfortable for patients.
"Today, we are one step closer to delivering that.
"We hope that in the near future, the Sonopill will be available to all patients as part of regular medical check-ups, effectively catching serious diseases at an early stage and monitoring the health of everyone's digestive system."
The Sonopill is a small capsule -- with a diameter of 21mm and length of 39mm, which the engineers say can be scaled down. The capsule houses a micro ultrasound transducer, an LED light, camera and magnet.
A very small flexible cable is tethered to the capsule which also passes into the body via the rectum and sends ultrasound images back to a computer in the examination room.
The feasibility tests were conducted on laboratory models and in animal studies involving pigs.
Diseases of the gastrointestinal tract account for approximately 8 million deaths a year across the world, including some bowel cancers which are linked with high mortality.
 

Story Source:
Materials provided by University of Leeds. Note: Content may be edited for style and length.
 

 

Courtesy: ScienceDaily

 

'Sneezing' plants contribute to disease proliferation

Virginia Tech researchers discovered that wheat plants "sneezing" off condensation can vastly impact the spread of spore-borne diseases, such as wheat leaf rust, which can cause crop yield losses of up to 20 percent or more in the United States and higher average losses in less developed agricultural nations.

The study, published June 19, and featured on the cover of the Journal of the Royal Society Interface, is part of a three-year grant obtained from the U.S. Department of Agriculture's National Institute of Food and Agriculture to study the dispersal of wheat pathogens by rain splash and jumping-droplet condensation.

Jonathan Boreyko, assistant professor of mechanical engineering in the College of Engineering is a co-principal investigator on the grant and David Schmale, professor of plant pathology, physiology, and weed science in the College of Agriculture and Life Sciences, is the primary investigator of the nearly $500,000 project.
"Professor Schmale had seen some of the work we've been doing on condensation and was curious to see what we could learn about condensation on wheat leaves," said Boreyko. "The project didn't start with any expectations, but people already knew that rain splash and wind caused pathogenic spores to be removed from plants and spread to others, and we wanted to see if condensation might also have a role to play in spore dispersal."
The students involved in the study were told not to expect jumping droplets in their condensation tests, as the droplets are known to only occur on specific surfaces, namely superhydrophobic surfaces normally associated with exotic materials, such as lotus leaves and gecko skin. Superhydrophobic surfaces are non-wetting, and when spherical condensate grows, droplets merge together to release surface tension, which is converted into kinetic energy, which propels them from the surface.
"Conceptually, what the plants are doing is sneezing," Boreyko said. "The jumping droplets, at the rate of 100 or more an hour, are a violent expulsion of dew from the surface. It's good for the plant because it is removing spores from itself, but it's bad because, like a human sneeze, the liquid droplets are finding their way onto neighboring plants. Like a cold, it's easy to see how a single infected plant could propagate a disease across an entire crop."
The paper, co-first-authored by Saurabh Nath and Farzad Ahmadi, engineering mechanics graduate students in Boreyko's lab, showed the jumping droplets can dramatically increase the dispersal of disease spores.
"We wanted to find out, first if the condensation droplets can carry spores, and while 90 percent of them carry only a single spore, we have seen instances where a droplet has carried as many as 11," Ahmadi said. "We also looked at how high the spores can jump and whether they can get past the boundary layer of the leaf."
The boundary layer, which is about a millimeter thick, is the region of air near the leaf's surface where the wind doesn't affect the droplet. If the kinetic energy from merging moves the jumping droplet above the boundary layer, the droplet can be taken by the wind. Depending upon the wind speed, it's feasible for the droplet to then be moved great distances, including to neighboring fields or farms.
"Using water-sensitive paper we measured how high the droplets can jump," Ahmadi said. "A blue dot on the paper shows us a droplet, and a reddish dot shows us a spore, so in this way we can calculate both the height and the number of spores in the droplet."
The droplets in Ahmadi's tests routinely jumped from 2-5 millimeters from the surface of the leaf, well above the distance necessary to be taken by the wind to be re-deposited elsewhere.
"It's important to realize these droplets are microscopic in size," explained Boreyko. "Each droplet is about the same size as the thickness of a human hair -- about 50 micrometers -- so this is all happening at a scale we don't notice. A 0.1 meter per second wind can support the weight of a jumping droplet, whereas a droplet directly on the leaf requires a wind of 10 meters per second -- 100 times stronger to be removed. Once it's in the wind, there is, hypothetically, no limit to how far it can be carried."
The low wind speed needed to carry the droplets means that the spore-ridden dew drops can have a large impact on crop health over a very wide area. "We know now that wind and rain aren't the only factors in the spread of disease among crops," Boreyko said.
The next phase of the continuing experiment for Boreyko and his team is to see how far the wind can carry the spore-bearing droplets. Using water-sensitive paper spread out in varying distances from a wheat leaf, the team will use fans to simulate wind and collect data on droplet and spore dispersal.
 

Journal Reference:

1. Saurabh Nath, S. Farzad Ahmadi, Hope A. Gruszewski, Stuti Budhiraja, Caitlin E. Bisbano, Sunghwan Jung, David G. Schmale, Jonathan B. Boreyko. ‘Sneezing’ plants: pathogen transport via jumping-droplet condensation. Journal of The Royal Society Interface, 2019; 16 (155): 20190243 DOI: 10.1098/rsif.2019.0243 

Courtesy: ScienceDaily
 

Gut microbes eat our medication

The first time Vayu Maini Rekdal manipulated microbes, he made a decent sourdough bread. At the time, young Maini Rekdal, and most people who head to the kitchen to whip up a salad dressing, pop popcorn, ferment vegetables, or caramelize onions, did not consider the crucial chemical reactions behind these concoctions.

Pills illustration (stock image).

Credit: © georgejmclittle / Adobe Stock

Even more crucial are the reactions that happen after the plates are clean. When a slice of sourdough travels through the digestive system, the trillions of microbes that live in our gut help the body break down that bread to absorb the nutrients. Since the human body cannot digest certain substances -- all-important fiber, for example -- microbes step up to perform chemistry no human can.

"But this kind of microbial metabolism can also be detrimental," said Maini Rekdal, a graduate student in the lab of Professor Emily Balskus and first-author on their new study published in Science. According to Maini Rekdal, gut microbes can chew up medications, too, often with hazardous side effects. "Maybe the drug is not going to reach its target in the body, maybe it's going to be toxic all of a sudden, maybe it's going to be less helpful," Maini Rekdal said.

In their study, Balskus, Maini Rekdal, and their collaborators at the University of California San Francisco, describe one of the first concrete examples of how the microbiome can interfere with a drug's intended path through the body. Focusing on levodopa (L-dopa), the primary treatment for Parkinson's disease, they identified which bacteria are responsible for degrading the drug and how to stop this microbial interference.

Parkinson's disease attacks nerve cells in the brain that produce dopamine, without which the body can suffer tremors, muscle rigidity, and problems with balance and coordination. L-dopa delivers dopamine to the brain to relieve symptoms. But only about 1 to 5% of the drug actually reaches the brain.

This number -- and the drug's efficacy -- varies widely from patient to patient. Since the introduction of L-dopa in the late 1960s, researchers have known that the body's enzymes (tools that perform necessary chemistry) can break down L-dopa in the gut, preventing the drug from reaching the brain. So, the pharmaceutical industry introduced a new drug, carbidopa, to block unwanted L-dopa metabolism. Taken together, the treatment seemed to work.

"Even so," Maini Rekdal said, "there's a lot of metabolism that's unexplained, and it's very variable between people." That variance is a problem: Not only is the drug less effective for some patients, but when L-dopa is transformed into dopamine outside the brain, the compound can cause side effects, including severe gastrointestinal distress and cardiac arrhythmias. If less of the drug reaches the brain, patients are often given more to manage their symptoms, potentially exacerbating these side effects.

Maini Rekdal suspected microbes might be behind the L-dopa disappearance. Since previous research showed that antibiotics improve a patient's response to L-dopa, scientists speculated that bacteria might be to blame. Still, no one identified which bacterial species might be culpable or how and why they eat the drug.

So, the Balskus team launched an investigation. The unusual chemistry -- L-dopa to dopamine -- was their first clue.

Few bacterial enzymes can perform this conversion. But, a good number bind to tyrosine -- an amino acid similar to L-dopa. And one, from a food microbe often found in milk and pickles (Lactobacillus brevis), can accept both tyrosine and L-dopa.

Using the Human Microbiome Project as a reference, Maini Rekdal and his team hunted through bacterial DNA to identify which gut microbes had genes to encode a similar enzyme. Several fit their criteria; but only one strain, Enterococcus faecalis (E. faecalis), ate all the L-dopa, every time.

With this discovery, the team provided the first strong evidence connecting E. faecalis and the bacteria's enzyme (PLP-dependent tyrosine decarboxylase or TyrDC) to L-dopa metabolism.

And yet, a human enzyme can and does convert L-dopa to dopamine in the gut, the same reaction carbidopa is designed to stop. Then why, the team wondered, does the E. faecalis enzyme escape carbidopa's reach?

Even though the human and bacterial enzymes perform the exact same chemical reaction, the bacterial one looks just a little different. Maini Rekdal speculated that carbidopa may not be able to penetrate the microbial cells or the slight structural variance could prevent the drug from interacting with the bacterial enzyme. If true, other host-targeted treatments may be just as ineffective as carbidopa against similar microbial machinations.

But the cause may not matter. Balskus and her team already discovered a molecule capable of inhibiting the bacterial enzyme.

"The molecule turns off this unwanted bacterial metabolism without killing the bacteria; it's just targeting a non-essential enzyme," Maini Rekdal said. This and similar compounds could provide a starting place for the development of new drugs to improve L-dopa therapy for Parkinson's patients.

The team might have stopped there. But instead, they pushed further to unravel a second step in the microbial metabolism of L-dopa. After E. faecalis converts the drug into dopamine, a second organism converts dopamine into another compound, meta-tyramine.

To find this second organism, Maini Rekdal left behind his mother dough's microbial masses to experiment with a fecal sample. He subjected its diverse microbial community to a Darwinian game, feeding dopamine to hordes of microbes to see which prospered.

Eggerthella lenta won. These bacteria consume dopamine, producing meta-tyramine as a by-product. This kind of reaction is challenging, even for chemists. "There's no way to do it on the bench top," Maini Rekdal said, "and previously no enzymes were known that did this exact reaction."

The meta-tyramine by-product may contribute to some of the noxious L-dopa side effects; more research needs to be done. But, apart from the implications for Parkinson's patients, E. lenta's novel chemistry raises more questions: Why would bacteria adapt to use dopamine, which is typically associated with the brain? What else can gut microbes do? And does this chemistry impact our health?

"All of this suggests that gut microbes may contribute to the dramatic variability that is observed in side effects and efficacy between different patients taking L-dopa," Balskus said.

But this microbial interference may not be limited to L-dopa and Parkinson's disease. Their study could shepherd additional work to discover exactly who is in our gut, what they can do, and how they can impact our health, for better or worse.

Journal Reference:

1. Vayu Maini Rekdal, Elizabeth N. Bess, Jordan E. Bisanz, Peter J. Turnbaugh, Emily P. Balskus. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science, 2019; 364 (6445): eaau6323 DOI: 10.1126/science.aau6323 

Courtesy: ScienceDaily