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Medical Technologies

At the University of Minnesota, researchers have developed a soft robotic system that can ‘grow’ like a plant. The mechanism allows it to travel through difficult-to-access areas, such as the tortuous gastrointestinal tract or vasculature. The system works by extruding a liquid through an opening in the device, and at the same time a photopolymerization process results in the rapid solidification of the liquid into a solid structure. The device illuminates the extruded liquid monomers, triggering the photopolymerization. This process mimics the way plants incrementally add material to their growing tips and root tips. The researchers hope that the technology could provide soft robots that can more easily travel to difficult-to-reach parts of the body.

Soft robots are making in-roads in the medical sphere, with their ability to interact with our soft tissues without the risk of abrasion and damage that come with more rigid devices. However, just being soft may not be enough to access everywhere in the body. Some spaces are difficult to travel to, and many of the ‘thoroughfares’ through our body, such as the gastrointestinal tract and our vasculature, are extremely windy, making it challenging to safely maneuver a robotic system through them.

These researchers took inspiration from the way that plants grow to develop a technique that can help a soft robot to navigate tight spaces. “We were really inspired by how plants and fungi grow,” said Matthew Hausladen, a researcher involved in the study. “We took the idea that plants and fungi add material at the end of their bodies, either at their root tips or at their new shoots, and we translated that to an engineering system.”       

The device works by extruding a liquid out of a hole. As this occurs, the liquid monomer solution is activated using a light, triggering a photopolymerization process and resulting in a solid polymer ‘stalk’ that emerges from the back of the robot. This flexible and ever-growing stalk helps to push the robot through tight and winding spaces.  

The researchers hope that this technique could lead to new types of soft robots that have unique advantages in accessing difficult-to-reach areas in the body.

Here’s a demonstration of the device traversing a winding tube:

See a video below where one of the researchers discusses the concept:

Study in journal Proceedings of the National Academy of Sciences: Synthetic growth by self-lubricated photopolymerization and extrusion inspired by plants and fungi

Via: University of Minnesota

A team at the University of Illinois at Urbana-Champaign has developed a DNA net system that can ensnare Sars-CoV-2 and bind to the notorious spike protein. The nets contain aptamers that bind the spike protein and emit an intense fluorescent signal once they’re bound together to the protein. This signal can be easily measured using a handheld fluorimeter. The technology provides a rapid and accurate way to test for the presence of the virus, and the researchers report that it has similar sensitivity as the current gold-standard test, PCR. However, the technology is not just envisaged as diagnostic. The nets can bind and disable the virus, suggesting that they may also have therapeutic applications.

While the pandemic may be winding down, the risk of new variants is ever present. Moreover, no-one knows when the next pandemic will arise, so the technologies we develop now will doubtless help us when new viruses emerge. This latest technology could do just that, and it has the potential to be both diagnostic and therapeutic.

“This platform combines the sensitivity of PCR and the speed and low cost of antigen tests,” said Xing Wang, one of its developers. “We need tests like this for a couple of reasons. One is to prepare for the next pandemic. The other reason is to track ongoing viral epidemics — not only coronaviruses, but also other deadly and economically impactful viruses like HIV or influenza.”

The DNA nets created by these researchers can rapidly and inexpensively provide Sars-CoV-2 detection. The system involves a user mixing a patient sample with the DNA nets, and then employing a handheld fluorimeter to detect if the aptamers present have bound to the viral spike protein.

“I had this idea at the very beginning of the pandemic to build a platform for testing, but also for inhibition at the same time,” Wang said. “Lots of other groups working on inhibitors are trying to wrap up the entire virus, or the parts of the virus that provide access to antibodies. This is not good, because you want the body to form antibodies. With the hollow DNA net structures, antibodies can still access the virus.”

The system may be suitable for point-of-care use, as it does not require any specialized equipment and is relatively inexpensive, costing approximately $1.26 per test. The technology can also be easily adapted to help detect other viruses.

“Another advantage of this measure is that we can detect the entire virus, which is still infectious, and distinguish it from fragments that may not be infectious anymore,” said Wang. “This not only gives patients and physicians better understanding of whether they are infectious, but it could greatly improve community-level modeling and tracking of active outbreaks, such as through wastewater.”

Study in Journal of the American Chemical Society: Net-Shaped DNA Nanostructures Designed for Rapid/Sensitive Detection and Potential Inhibition of the SARS-CoV-2 Virus

Via: University of Illinois

Researchers at the University of California San Diego have developed a microrobot system to treat bacterial pneumonia. The microrobots consist of living algal cells that can swim very effectively in biological fluids, allowing them to navigate throughout the lungs and deliver drugs to difficult-to-reach areas. The algal cells are studded with antibiotic-loaded polymer spheres that are coated with cell membranes from neutrophils, which help them to neutralize inflammatory molecules that are released by bacteria in the lungs, providing a localized anti-inflammatory effect. In tests in mice with bacterial pneumonia, the microrobots helped to clear the infection. All the treated mice survived for at least 30 days, whereas untreated mice died within three days.

Bacterial pneumonia can have dire consequences for patients, particularly since it can often develop when someone is mechanically ventilated and already in a serious condition. It can also be difficult to treat. Simply administering large doses of antibiotics into the blood stream may not work so well, as very little of the dose ends up where it is needed in the lungs.

There is a need for more targeted and effective therapies. This prompted these UCSD researchers to create a localized therapy that can actively swim into the lungs and deliver drugs exactly where they are needed. “Our goal is to do targeted drug delivery into more challenging parts of the body, like the lungs,” said Liangfang Zhang, one of the creators of the new microrobots. “And we want to do it in a way that is safe, easy, biocompatible and long lasting. That is what we’ve demonstrated in this work.”    

Colored SEM image of a pneumonia-fighting microrobot made of an algae cell (green) covered with biodegradable polymer nanoparticles (brown). The nanoparticles contain antibiotics and are coated with neutrophil cell membranes. Images credit: Credit: Wang lab/UC San Diego, Fangyu Zhang and Zhengxing Li

The researchers chose algae as a delivery vehicle for antibiotics. The algal cells are highly adept at swimming through biological fluids, such as the thick mucus that is typically present in the lungs of someone with pneumonia. They attached antibiotic-loaded polymer spheres to the outside of the algal cells, and also coated the spheres in neutrophil membranes for added anti-inflammatory action.

They tested the microrobots in mice with pneumonia caused by Pseudomonas aeruginosa. This type of pneumonia tends to occur in patients who have undergone mechanical ventilation, and it can be life-threatening. The team delivered the microrobots into the lungs using a tube inserted into the trachea. In the treated mice, the infection cleared up after a week, and all survived, whereas the untreated mice died in as little as three days. The approach was also more effective than IV antibiotics, requiring a fraction of the dose to effectively treat the infection.  

“With an IV injection, sometimes only a very small fraction of antibiotics will get into the lungs. That’s why many current antibiotic treatments for pneumonia don’t work as well as needed, leading to very high mortality rates in the sickest patients,” said Victor Nizet, another researcher involved in the study. “Based on these mouse data, we see that the microrobots could potentially improve antibiotic penetration to kill bacterial pathogens and save more patients’ lives.”

Study in Nature Materials: Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia

Via: UCSD

Scientists at Duke University have developed a ‘nanorattle’ system that allows for the detection of mRNA biomarkers of cancer. The tiny structures consist of gold nanospheres with a surrounding silver nanocage, forming the so-called rattle. The nanorattles are also loaded with light scattering dyes called Raman reporters. When illuminated with a laser, the rattles emit significant amounts of light. The researchers developed the technology so that they could detect mRNA biomarkers of cancer, which will bind to the nanorattles if present in a patient sample. The researchers can then use a laser to illuminate the nanorattles to see if the biomarkers are present. The entire system fits into a lab-on-a-stick device, potentially allowing for point-of-care diagnostics in low-resource regions.  

Head and neck cancers have a relatively poor survival rate of 40-60% in many regions of the world, in part because of a lack of early detection. This prompted these researchers to attempt to design a point of care diagnostic system for such cancers, potentially letting healthcare workers to perform such diagnostic tests simply and quickly.

“In low-resource settings, these cancers often present in advanced stages and result in poor outcomes due in part to limited examination equipment, lack of trained healthcare workers and essentially non-existent screening programs,” said Walter Lee, one of the lead researchers on this project. “Having the ability to detect these cancers early should lead to earlier treatment and improvement in outcomes, both in survival and quality of life. This approach is exciting since it does not depend on a pathologist review and potentially could be used at the point of care.”

The system is designed to help detect mRNA biomarkers. Many patients with head and neck cancers will have upregulated levels of certain mRNA markers. The researchers designed their system so that the nanorattles will bind to such mRNA sequences. They also included magnetic beads in their lab-on-a-stick device that can also bind to the same mRNA sequences.

Consequently, the procedure involves adding a patient mRNA sample to the device and allowing the mRNA biomarker sequences to bind to the magnetic beads. Then, a sample of nanorattles is added to the device, and they will bind to the now immobilized mRNA sequences, with the mRNA essentially forming a tether between the magnet and the nanorattle.

After a washing step to remove unbound nanorattles, the clinician can then use a handheld device to illuminate the bound nanorattles and see if any light is emitted by them, highlighting the presence of the mRNA biomarkers.

Study in Journal of Raman Spectroscopy: Machine learning using convolutional neural networks for SERS analysis of biomarkers in medical diagnostics

Via: Duke

Scientists at the University of New South Wales in Australia have developed a method to produce human blood stem cell precursors from human pluripotent stem cells. The method may have use in treating cancer patients who require high doses of such blood stem cells to help replenish endogenous populations that have been destroyed by chemotherapy.

The researchers exploited the tendency of cells to respond to mechanical stimuli and cultured the pluripotent stem cells in a microfluidic device that mimicked the pulsatile flow of the embryonic heartbeat. Given that human blood stem cells naturally form during embryonic development, the Australian team hypothesized that mimicking these conditions in vitro would help the cells to develop as blood stem cells.     

Chemotherapy can have pretty devastating effects on blood cells and the stem cells that differentiate to produce them. There is a current shortage of donor stem cells to assist such patients, and researchers have struggled to create suitable stem cells in the lab.

Creating induced pluripotent stem cells from adult human cells has been an important step along the way in that it helps to avoid the need for embryonic cells or cells from animals. However, getting such cells to reliably turn into human blood stem cells that can then differentiate into any type of blood cell has been a challenge.

To address this, these researchers have turned to a microfluidic device to see if they could use mechanical stimuli to persuade induced pluripotent stem cells to turn into blood stem cells, or at least advance them somewhat down that path. The device mimics the pulsatile flow of the embryonic heartbeat, doubtless an important stimulus for cells within the developing embryo.

“Part of the problem is that we still don’t fully understand all the processes going on in the microenvironment during embryonic development that leads to the creation of blood stem cells at about day 32 in the embryonic development,” said Jingjing Li, one of the leaders of the project. “So we made a device mimicking the heart beating and the blood circulation and an orbital shaking system which causes shear stress — or friction — of the blood cells as they move through the device or around in a dish.”    

So far, the researchers have shown that the device can stimulate the cells to develop into blood stem cell precursors. These cells can then go on to differentiate into any kind of blood cell. The team hopes to scale the technique up to work in a bioreactor, allowing them to produce large numbers of cells.

“Blood stem cells used in transplantation require donors with the same tissue-type as the patient,” said Robert Nordon, another researcher involved in the study. “Manufacture of blood stem cells from pluripotent stem cell lines would solve this problem without the need for tissue-matched donors providing a plentiful supply to treat blood cancers or genetic disease.”

Study in journal Cell Reports: Mimicry of embryonic circulation enhances the hoxa hemogenic niche and human blood development

Via: University of New South Wales

Scientists at Shanghai Tongji University in China have created a face mask that can alert the wearer to the presence of respiratory viruses in the surrounding environment, including the viruses behind COVID-19 and influenza. The mask includes aptamers, which are short sequences of DNA or RNA that can bind to protein targets. When viral particles bind to the aptamers, ion-gated transistors boost the signal so that the mask can sensitively detect small amounts of virus. The mask sends a message to the wearer’s smartphone within 10 minutes of detecting the virus. The technology could be very valuable for healthcare staff or vulnerable patients who are at high risk of severe disease.

Face masks have been a cornerstone in our response to the COVID-19 pandemic. The simple and effective barrier function such masks fulfill has doubtless helped to limit the spread of SARS‑CoV‑2. However, what if our masks could do much more, providing us with an early warning system that viral contamination is in the air?

“Previous research has shown face mask wearing can reduce the risk of spreading and contracting the disease,” said Yin Fang, a researcher involved in the study. “So, we wanted to create a mask that can detect the presence of virus in the air and alert the wearer.”

The team behind this latest study has created just that. Their mask does not just detect SARS‑CoV‑2, but it can also identify two different strains of influenza (H5N1, and H1N1). With the southern hemisphere experiencing a significant resurgence of flu this year, after two years without much flu activity, such technologies could be helpful for vulnerable patients who could experience serious complications if they were to contract flu or COVID-19.

The mask relies on aptamers, which are synthetic molecules made using DNA or RNA, but which function somewhat like antibodies, binding specific molecules such as proteins. The aptamers in the mask are specific for SARS‑CoV‑2, H5N1, and H1N1. If such viral particles are present in the air around the mask wearer, they will bind to the aptamers in the mask. Ion-gated transistors present in the mask sensor then help to boost this signal, allowing the mask to take highly sensitive measurements.

The mask will then send a signal to the wearer’s smartphone within 10 minutes to alert them to the presence of viral particles. The researchers are working on reducing this time, to help make the system as quick and useful as possible.

Study in journal Matter: Wearable bioelectronic masks for wireless detection of respiratory infectious diseases by gaseous media

Via: Cell Press

At the University of Washington a research team has developed a smartphone system that can measure blood oxygen levels. The technology uses the camera and flash of the phone to take the measurement, and the system is so easy to use that it may be well suited for at-home use. A person presses their finger over the camera, which gets illuminated by the flash, and the camera measures how much light from the flash the finger absorbs, which a deep-learning algorithm can then correlate with blood oxygen levels. The system could be useful for COVID-19 patients who wish to monitor their progress at home and receive early warning of any disease exacerbation.   

Healthy individuals typically have a blood oxygen saturation of 95% and higher, but respiratory illnesses that make our lungs work less efficiently, such as COVID-19, can result in this number declining, with an associated need for medical attention. At present, clinicians can easily measure blood oxygen levels with a clip-on pulse oximeter, which is affixed to the finger or ear.

However, giving people the ability to measure their blood oxygen levels at home would be beneficial. These researchers have developed a technique that allows people to do just that, using a tool most of us possess already, the smartphone.

Images credit: Dennis Wise/University of Washington

“This way you could have multiple measurements with your own device at either no cost or low cost,” said Matthew Thompson, one of the developers of the new technology. “In an ideal world, this information could be seamlessly transmitted to a doctor’s office. This would be really beneficial for telemedicine appointments or for triage nurses to be able to quickly determine whether patients need to go to the emergency department or if they can continue to rest at home and make an appointment with their primary care provider later.”

To train the deep learning algorithm, the researchers recruited volunteers who wore a standard pulse oximeter on one finger and pressed another finger against a smartphone camera. This allowed the researchers to correlate the readings between the two devices. Then the volunteers breathed a mixture of oxygen and nitrogen for 15 minutes, which caused their blood oxygen levels to drop. Once the algorithm was trained, the smartphone system could identify that people had low blood oxygen levels approximately 80% of the time.

“Other smartphone apps that do this were developed by asking people to hold their breath. But people get very uncomfortable and have to breathe after a minute or so, and that’s before their blood-oxygen levels have gone down far enough to represent the full range of clinically relevant data,” said Jason Hoffman, another researcher involved in the study. “With our test, we’re able to gather 15 minutes of data from each subject. Our data shows that smartphones could work well right in the critical threshold range.”

Study in journal npj Digital Medicine: Smartphone camera oximetry in an induced hypoxemia study

Flashback: Smartphone Camera Detects Breathing Rate, Pulse and Blood Oxygen Saturation

Via: University of Washington

At the University of Minnesota a team of researchers has developed a 3D printed light sensing wearable that can help people with light-sensitive diseases, such as lupus, to understand more about the types of light that can exacerbate their symptoms. Many people with lupus are sensitive to light, such as sunlight or even regular indoor light, but they may not know what specific light conditions are likely to cause flare-ups. This new device aims to provide such people with more information, so that they can learn more about their flare-ups and take steps to avoid or reduce them. The technology could lead to more personalized medicine and a greater understanding of light-sensitive disease.

Approximately five million people worldwide live with lupus and between 40-70% of those experience some form of light sensitivity. These can include rashes, fatigue, and joint pain. This light sensitivity seems to vary from patient to patient, making it difficult to provide advice on which situations to avoid and how to reduce the likelihood of light-mediated flare-ups.

“I treat a lot of patients with lupus or related diseases, and clinically, it is challenging to predict when patients’ symptoms are going to flare,” said David Pearson, one of the creators of the new device. “We know that ultraviolet light and, in some cases visible light, can cause flares of symptoms — both on their skin, as well as internally — but we don’t always know what combinations of light wavelengths are contributing to the symptoms.”

In an effort to, ahem, shed more light on this situation, these researchers have developed a wearable light sensor that can help patients and their caregivers better correlate light conditions with flare-ups. The fully 3D printed device contains zinc oxide, which can convert a UV light stimulus to an electrical signal. The device is built on a silicone base, and contains optical filters that can be swapped out depending on the type of light that is intended to be measured.

“There is no other device like this right now with this potential for personalization and such easy fabrication,” said Pearson. “The dream would be to have one of these 3D printers right in my office. I could see a patient and assess what light wavelengths we want to evaluate. Then I could just print it off for the patient and give it to them. It could be 100 percent personalized to their needs. That’s where the future of medicine is going.”

See a video about the technology below.

Study in Advanced Science: 3D Printed Skin‐Interfaced UV‐Visible Hybrid Photodetectors

Via: University of Minnesota

Researchers at the City University of Hong Kong have developed a magnetic soft millirobot that can grab and release objects, and move around by rolling. The device can be controlled using magnetic fields, and consists of a biodegradable gelatin and iron oxide microparticles.

The technology has significant potential as a minimally invasive drug delivery system, perhaps in the gastrointestinal tract, and may even lead to soft robots that can carry out surgical procedures within the body. One of the nicest features of the device is its rapid biodegradation over the space of a couple of days, which means that it may not have to be retrieved after serving its function in the body, instead breaking down into harmless constituents.    

Soft robots are the icky and ever so slightly disturbing cousins of their more traditional rigid counterparts. While they may appear to resemble a sea creature from the darkest depths of an ocean trench, they have enormous potential as a medical technology, with the ability to interact with our soft tissues without causing damage. In the fields of drug delivery and minimally invasive surgery, these robots could provide a sophisticated means to access and treat areas of the body that would otherwise be tricky to target.  

This latest offering is an early iteration of such technologies. The new millirobots are approximately as wide as a finger, and bear an uncanny resemblance to the aforementioned sea creature. They include an insect-like claw that can grab and transport objects. The robots can move by rolling and folding, and can navigate their way through body cavities, such as the gastrointestinal tract.      

Consisting of a natural material, gelatin, the millirobots can biodegrade in as little as two days in water, paving the way for medical procedures that do not require a follow-up surgical procedure to remove the millirobot afterwards.

Iron oxide microparticles within the gelatin structure make the robot highly responsive to magnetic fields, allowing it to be manipulated. The magnetic fields cause the microparticles to pull and distend the gelatin structure, resulting in ‘legs’ that can bend and move.  

So far, the Hong Kong researchers tested the technology as a drug delivery device, coating it in a drug solution and then using magnetic fields to move it through a model of the gastrointestinal system. When the robot reached the target region of the ‘gut’ it unfurled, releasing the drug.

See a video about the system below.

Study in ACS Applied Polymer Materials: Soft Tunable Gelatin Robot with Insect-like Claw for Grasping, Transportation, and Delivery

Via: American Chemical Society

Researchers at the Harbin Institute of Technology in China have developed a microfluidic-style chip that models the alveoli present in our airways. The tiny air sacs in our lungs are crucial for gas exchange, but they can be difficult to study and model. A better understanding of airflow patterns in these structures could be very useful in informing the design of inhalable medications, understanding respiratory threats in the form of inhaled particulate pollutants, and also in understanding respiratory diseases. This new device models a branching point of the airways using a flexible polymer that has been molded into small tubes that mimic the alveoli. A glass layer allows the researchers to visualize flow through the device, while a small pump creates rhythmic changes in air pressure to mimic breathing.     

Respiratory disease has been in our minds over the past two years. Getting better at fighting it will involve understanding it better. Moreover, if we are to develop new treatments, such as new inhalable medications, it is best if we know what drug properties, such as particle size and shape, are best to achieve maximal uptake and effects in the lungs.   

This latest technology could help to cast a little light on these processes by modeling alveoli and their air flow patterns during breathing. It could also be modified to help model airflow in various respiratory diseases, such as COPD. It is essentially a small portion of the bronchial tree that has been modeled on a chip. The chip is multi-layered, and the upper layer contains small tubes that were molded from a flexible polymer. The polymer has been arranged so that it mimics a branching structure within the airways and several alveoli.

The lower portion of the chip is glass, which allows the researchers to view the air flow through the polymer structure. The chip can be attached to a pump and the air within it pressurized in a rhythmic fashion to mimic breathing. The researchers also added some small colored polystyrene spheres, which move as the chip is pressurized, allowing the researchers to study the airflow patterns within the structure.  

Successive branches within the airways are called generations, and alveoli appear at the fifteenth generation and persist until the twenty third generation. The new technology has already yielded some new insights about air flow patterns in the lungs and differences between generations.

“The alveolar flow pattern of the 19th generation is dominated by vortex flow,” said Yonggang Zhu, a researcher involved in the study. “Alveolar flow patterns in the 20th generation are similar to those in the 19th, but somewhat compressed. The alveolar flow pattern in the 21st generation has both vortex flow and radial flow. The vortex region is much smaller than the radial flow region. By the time the flow reaches the 22nd generation, vortex flow disappears completely, and we observe only radial flow.”     

Study in journal Biomicrofluidics: Microflows in two-generation alveolar cells at an acinar bifurcation

Via: American Institute of Physics

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