NanoRobots Deliver Antibiotics and Improve Dramatically Survival Rate

Tiny robots made of algae are swimming through the lung fluids of mice, delivering antibiotics straight to the bacteria that cause a deadly form of pneumonia. It’s happening now in UC San Diego ( UCSD) labs and it shows the tremendous potential of microrobotics. Nanoparticles, loaded with medicine, are attached to the microrobots and introduced into the lungs.

Microscopic and colorized view of an algae robot covered with drug-carrying particles

“They can actively swim in the body fluid, dip into the thick part of the tissue and carry a lot of these therapeutic payloads to the disease site, and then very effectively kill the bacteria,” said professor of nanoengineering Liangfang Zhang, one of the lead researchers.

Zhang said the results of the experiment were dramatic. The mice treated with drugs in a conventional way died within days.

But when we loaded the drugs into our formulation — the nanoparticle and the algae system — we found that all the animals survived,” he said. “We achieved a remarkable 100% survival rate from the study.

Anyone who has swallowed an aspirin knows one very conventional way of delivering drugs. The medication is ingested and is carried throughout the body. “You take the pill and it’s all passive. The drug goes slowly by diffusion,” explained Joseph Wang, a distinguished professor of nanoengineering at UC San Diego. “By having dynamic active delivery, we are accelerating targeted delivery to the right location.”

Wang’s lab at UCSD shows many examples of microrobots, designed to navigate the body’s channels and cavities. The algae robot is organic, and swims with its flagella. Another robot, made from zinc, reacts with gastric fluid and generates hydrogen gas, which propels it like a true rocket.

Wang points out the algae robot is not attracted to the bacteria, but they move so effectively through the fluids of the lung that it greatly improves the dispersion of the drug. Wang has actually loaded robots into pills, including aspirin. “This we showed with pigs, actually, and showed that when you have the active delivery there is much better uptake by the blood,” Wang said.

The purpose of the research, of course, is not to treat pigs or mice, but humans. Zhang said the study of algae robots in the lungs is very innovative and experimental, and human trials are still a ways away.

We demonstrated the feasibility of the technology and what I foresee is, we need to study more to demonstrate the efficacy in large animal species,” he added, “before we can translate it to a human study.”


Sticker on the Skin Provides Clear Image of Heart, Lungs

Ultrasound imaging is a safe and noninvasive window into the body’s workings, providing clinicians with live images of a patient’s internal organs. To capture these images, trained technicians manipulate ultrasound wands and probes to direct sound waves into the body. These waves reflect back out to produce high-resolution images of a patient’s heart, lungs, and other deep organs.

Currently, ultrasound imaging requires bulky and specialized equipment available only in hospitals and doctor’s offices. But a new design by MIT engineers might make the technology as wearable and accessible as buying Band-Aids at the pharmacy. In a paper appearing today in Science, the engineers present the design for a new ultrasound sticker — a stamp-sized device that sticks to skin and can provide continuous ultrasound imaging of internal organs for 48 hours.

The researchers applied the stickers to volunteers and showed the devices produced live, high-resolution images of major blood vessels and deeper organs such as the heart, lungs, and stomach. The stickers maintained a strong adhesion and captured changes in underlying organs as volunteers performed various activities, including sitting, standing, jogging, and biking. The current design requires connecting the stickers to instruments that translate the reflected sound waves into images. The researchers point out that even in their current form, the stickers could have immediate applications: For instance, the devices could be applied to patients in the hospital, similar to heart-monitoring EKG stickers, and could continuously image internal organs without requiring a technician to hold a probe in place for long periods of time.

If the devices can be made to operate wirelessly — a goal the team is currently working toward — the ultrasound stickers could be made into wearable imaging products that patients could take home from a doctor’s office or even buy at a pharmacy.

We envision a few patches adhered to different locations on the body, and the patches would communicate with your cellphone, where AI algorithms would analyze the images on demand,” says the study’s senior author, Xuanhe Zhao, professor of mechanical engineering and civil at MIT. “We believe we’ve opened a new era of wearable imaging: With a few patches on your body, you could see your internal organs.

The study also includes lead authors Chonghe Wang and Xiaoyu Chen, and co-authors Liu Wang, Mitsutoshi Makihata, and Tao Zhao at MIT, along with Hsiao-Chuan Liu of the Mayo Clinic in Rochester, Minnesota.


Ravaged Landscape of COVID-19 Lungs

A revolutionary tool designed to broaden our understanding of human anatomy has for the first time provided scientists with a cellular-level look at lungs damaged by COVID-19. In healthy lungs, the blood vessel system that oxygenates the blood is separate from the system that feeds the lung tissue itself. But in some severe respiratory illnesses, such as pneumonia, pressures caused by the infection can lead blood vessels in the heart and lungs to expand and grow, sometimes cutting through the body and forming channels between parts of the pulmonary system that shouldn’t be connected. Similarly, COVID-19 infections can create the same types of abnormal channels. The channels give unoxygenated blood coming into the lungs an alternate exit ramp, allowing it to essentially skip the line and shoot back into the body without picking up any oxygen molecules first. Scientists believed that this could be a cause of the low blood oxygen levels sometimes experienced by COVID-19 patients, a condition known as hypoxemia.

Blood vessel growth is a very controlled process,” said Claire Walsh, a medical engineer at University College London and the first author of the imaging study, published in the journal Nature Methods. “It should be in this lovely tree-like branching structure. And you look at the COVID lungs, and you can just see it’s in these big clumps of really dense vessels all over the place, so that it just looks … wrong.

Walsh’s team, which included clinicians from Germany and France, has procured sharper-than-ever images of these warped structures, thanks to an imaging technique known as HiP-CT, or Hierarchical Phase-Contrast Tomography, which allows them to zoom in on any body part with 100 times the resolution of a traditional CT scan. Although the technique can only be used to capture images of samples removed from a body and preserved in a way that minimizes interference (rather than of organs that are still part of a living person), in pairing it with the world’s brightest X-rays at the European Synchrotron particle accelerator, the researchers hope to build a visual database of not only lungs infected with COVID-19, but other, healthy organs throughout the body.


How The Coronavirus Infects Human Cells

Tiny artificial lungs grown in a lab from adult stem cells have allowed scientists to watch how coronavirus infects the lungs in a new ‘major breakthrough‘. Researchers from Duke University and Cambridge University produced artificial lungs in two independent and separate studies to examine the spread of Covid-19. The ‘living lung‘ models minimic the tiny air sacs that take up the oxygen we breathe, known to be where most serious lung damage from the deadly virus takes place.   Having access to the models to test the spread of SAS-CoV-2, the virus responsible for Covid-19, will allow researchers to test potential drugs and gain a better understanding of why some people suffer from the disease worse than others.

In both studies the 3D min-lung models were grown from stem cells that repair the deepest portions of the lungs when SARS-CoV-2 attacks – known as alveolar cells. To date, there have been more than 40 million cases of COVID-19 and almost 1.13 million deaths worldwide. The main target tissues of SARS-CoV-2, especially in patients that develop pneumonia, appear to be alveoli, according to the Cambridge team. They extracted the alveoli cells from donated tissue and reprogrammed them back to their earlierstem cell‘ stage and forced them to grow into self-organising alveolar-like 3D structures that mimic the behaviour of key lung tissue. Dr Joo-Hyeon Lee, co-senior author of the Cambridge paper, said we still know surprisingly little about how SARS-CoV-2 infects the lungs and causes disease.

Representative image of three – dimensional human lung alveolar organoid produced by the Cambridge and Korean researchers to better understand SARS-CoV-2

Our approach has allowed us to grow 3D models of key lung tissue – in a sense, “mini-lungs” – in the lab and study what happens when they become infected.’

Duke researchers took a similar approach. The team, led by Duke cell biologist Purushothama Rao Tata, say their model will allow for hundreds of experiments to be run simultaneously to screen for new drug candidates. ‘This is a versatile model system that allows us to study not only SARS-CoV-2, but any respiratory virus that targets these cells, including influenza,‘ Tata said.

Both teams infected models with a strain of SARS-CoV-2 to better understand who the virus spreads and what happens in the lung cells in response to the disease. The Cambridge team worked with researchers from South Korea to take a sample of the virus from a patient who was infected in January after travelling to Wuhan. Using a combination of fluorescence imaging and single cell genetic analysis, they were able to study how the cells responded to the virus.

When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly, reaching full cellular infection just six hours after infectionReplication enables the virus to spread throughout the body, infecting other cells and tissue, explained the Cambridge research team. Around the same time, the cells began to produce interferonsproteins that act as warning signals to neighbouring cells, telling them to activate their defences. After 48 hours, the interferons triggered the innate immune response – its first line of defence – and the cells started fighting back against infectionSixty hours after infection, a subset of alveolar cells began to disintegrate, leading to cell death and damage to the lung tissue.


Machine Learning Predicts Heart Failure

Every year, roughly one out of eight U.S. deaths is caused at least in part by heart failure. One of acute heart failure’s most common warning signs is excess fluid in the lungs, a condition known as “pulmonary edema.” A patient’s exact level of excess fluid often dictates the doctor’s course of action, but making such determinations is difficult and requires clinicians to rely on subtle features in X-rays that sometimes lead to inconsistent diagnoses and treatment plans.

To better handle that kind of nuance, a group led by researchers at MIT’s Computer Science and Artificial Intelligence Lab (CSAIL) has developed a machine learning model that can look at an X-ray to quantify how severe the edema is, on a four-level scale ranging from 0 (healthy) to 3 (very, very bad). The system determined the right level more than half of the time, and correctly diagnosed level 3 cases 90 percent of the time.

Working with Beth Israel Deaconess Medical Center (BIDMC) and Philips, the team plans to integrate the model into BIDMC’s emergency-room workflow this fall.

This project is meant to augment doctors workflow by providing additional information that can be used to inform their diagnoses as well as enable retrospective analyses,” says PhD student Ruizhi Liao, who was the co-lead author of a related paper with fellow PhD student Geeticka Chauhan and MIT professors Polina Golland and Peter Szolovits.

The team says that better edema diagnosis would help doctors manage not only acute heart issues, but other conditions like sepsis and kidney failure that are strongly associated with edema.

As part of a separate journal article, Liao and colleagues also took an existing public dataset of X-ray images and developed new annotations of severity labels that were agreed upon by a team of four radiologists. Liao’s hope is that these consensus labels can serve as a universal standard to benchmark future machine learning development.

An important aspect of the system is that it was trained not just on more than 300,000 X-ray images, but also on the corresponding text of reports about the X-rays that were written by radiologists. “By learning the association between images and their corresponding reports, the method has the potential for a new way of automatic report generation from the detection of image-driven findings,says Tanveer Syeda-Mahmood, a researcher not involved in the project who serves as chief scientist for IBM’s Medical Sieve Radiology Grand Challenge. “Of course, further experiments would have to be done for this to be broadly applicable to other findings and their fine-grained descriptors.”

Chauhan, Golland, Liao and Szolovits co-wrote the paper with MIT Assistant Professor Jacob Andreas, Professor William Wells of Brigham and Women’s Hospital, Xin Wang of Philips, and Seth Berkowitz and Steven Horng of BIDMC.


Non Invasive Breathing Aid From Mercedes Formula One

A new version of a breathing aid that can help coronavirus patients has been developed in less a week by a team involving Mercedes Formula One, and is being trialed at London hospitals.

Continuous Positive Airway Pressure (CPAP) devices have been used in China and Italy to deliver air and oxygen under pressure to patients’ lungs to help them breathe without the need for them to go on a ventilator, a more invasive process.

The new CPAP has already been approved by the relevant regulator and now 100 of the machines will be delivered to University College London Hospital (UCLH) for trials, before being rolled out to other hospitals.

Reports from Italy indicate that approximately 50% of patients given CPAP have avoided the need for invasive mechanical ventilation, which involves patients being sedated, freeing up ventilators for those more in need.


These devices will help to save lives by ensuring that ventilators, a limited resource, are used only for the most severely ill,” UCLH critical care consultant Professor Mervyn Singer said in a statement.

We hope they will make a real difference to hospitals across the UK by reducing demand on intensive care staff and beds, as well as helping patients recover without the need for more invasive ventilation.”