Scientists at EPFL and ETHZ have developed a new method for building microrobots that could be used in the body to deliver drugs and perform other medical operations.
For the past few years, scientists around the world have been studying ways to use miniature robots to better treat a variety of diseases. The robots are designed to enter the human body, where they can deliver drugs at specific locations or perform precise operations like clearing clogged-up arteries. By replacing invasive, often complicated surgery, they could optimize medicine.
EPFL scientist Selman Sakar teamed up with Hen-Wei Huang and Bradley Nelson at ETHZ to develop a simple and versatile method for building such bio-inspired robots and equipping them with advanced features. They also created a platform for testing several robot designs and studying different modes of locomotion. Their work produced complex reconfigurable microrobots that can be manufactured with high throughput. They built an integrated manipulation platform that can remotely control the robots’ mobility with electromagnetic fields, and cause them to shape-shift using heat.
Unlike conventional robots, these microrobots are soft, flexible, and motor-less. They are made of a biocompatible hydrogel and magnetic nanoparticles. These nanoparticles have two functions. They give the microrobots their shape during the manufacturing process, and make them move and swim when an electromagnetic field is applied.
Building one of these microrobots involves several steps. First, the nanoparticles are placed inside layers of a biocompatible hydrogel. Then an electromagnetic field is applied to orientate the nanoparticles at different parts of the robot, followed by a polymerization step to ‘solidify’ the hydrogel. After this, the robot is placed in water where it folds in specific ways depending on the orientation of the nanoparticles inside the gel, to form the final overall 3D architecture of the microrobot.
Once the final shape is achieved, an electromagnetic field is used to make the robot swim. Then, when heated, the robot changes shape and ‘unfolds’. This fabrication approach allowed the researchers to build microrobots that mimic the bacterium that causes African trypanosomiasis, otherwise known as sleeping sickness. This particular bacterium uses a flagellum for propulsion, but hides it away once inside a person’s bloodstream as a survival mechanism.
The researchers tested different microrobot designs to come up with one that imitates this behaviour. The prototype robot presented in this work has a bacterium-like flagellum that enables it to swim. When heated with a laser, the flagellum wraps around the robot’s body and is ‘hidden’.
‘We show that both a bacterium’s body and its flagellum play an important role in its movement,’ said Sakar. ‘Our new production method lets us test an array of shapes and combinations to obtain the best motion capability for a given task. Our research also provides valuable insight into how bacteria move inside the human body and adapt to changes in their microenvironment.’
For now, the microrobots are still in development. ‘There are many factors we have to take into account,’ says Sakar. ‘For instance, we have to make sure that the microrobots won’t cause any side-effects in patients.’

EPFL http://tinyurl.com/zg3rssf

Researchers working in four labs at UT Southwestern Medical Center have found a chink in a so-called ‘un-druggable’ lung cancer’s armour – and located an existing drug that might provide a treatment.

The study describes how the drug Selinexor (KPT-330) killed lung cancer cells and shrank tumours in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene. Selinexor is already in clinical trials for treatment of other types of cancer, primarily leukaemia and lymphoma but also gynaecological, brain, prostate, and head and neck cancers.

Lung cancer is the No. 1 cancer killer in the U.S., responsible for more than 158,000 deaths a year, according to the National Cancer Institute (NCI), and the KRAS oncogene is believed to be responsible for about 25 percent of all lung cancer cases. The 5-year survival rate for lung cancer is below 18 percent.

Cancers caused by the KRAS mutation have been a target for researchers since the mutation was discovered in humans in 1982. But, due in part to this oncogene’s almost impervious spherical shape, no one was able to find an opening for attack, said Dr. Pier Scaglioni, Associate Professor of Internal Medicine at UT Southwestern and a contributing author to the study.

Dr. Michael A. White, Adjunct Professor of Cell Biology and senior author of the study, assembled multiple research teams and used robotic machines to create and sift through trays with thousands of cancer cell/potential drug combinations to uncover the KRAS mutation’s weakness.

The scientists found that targeting and inactivating the protein XPO1, found in the cell nucleus and used to transport gene products from the nucleus to the cytoplasm, killed most of the KRAS mutant cancer cells.

‘We found that inhibiting the XPO1 gene kills lung cancer cells that are dependent on KRAS,’ Dr. Scaglioni said. ‘The unexpected coincidence here is that there is an existing drug that will inhibit XPO1.’

‘We know that this drug hits the XPO1 target in people,’ added Dr. White, also a research executive at Pfizer Inc. ‘But we will not know whether the drug will be effective until clinical trials are done, which should be completed in about two years.’

Based on the results of this study, Selinexor, developed by Karyopharm Therapeutics, will be the focus of a multi-centre lung cancer clinical trial led by UT Southwestern’s Dr. David Gerber, Associate Professor of Internal Medicine. That trial is expected to open for enrolment next year.

UT Southwestern Medical Center www.utsouthwestern.edu/newsroom/news-releases/year-2016/september/kras-cancer-white.html

Benzodiazepines and related drugs are initiated frequently in persons with Alzheimer’s disease already before the diagnosis, and their use becomes even more common after the diagnosis, shows a recent study from the University of Eastern Finland. Benzodiazepines and related drugs are used as a sleep medication and for anxiolytic purposes. These drugs were initiated more frequently in persons with Alzheimer’s disease than in persons not diagnosed with AD. Compared to persons not diagnosed with AD, it was three times more likely for persons with Alzheimer’s disease to initiate benzodiazepine use after the diagnosis, and benzodiazepines were most commonly initiated six months after the diagnosis.

The findings are based on data from the Finnish Medication Use and Alzheimer’s Disease Study, Medalz. Medalz comprises nationwide, extensive register-based data from the Finnish health care registers, and it includes all persons diagnosed with Alzheimer’s disease in Finland between 2005 and 2011. The study, analysed the initiation of benzodiazepines and related drugs in 51,981 persons diagnosed with AD. Their use of drugs was monitored for a period of five years, and the follow-up started already two years before the diagnosis. The findings were compared to persons not diagnosed with Alzheimer’s disease who were matched based on age and gender.

According to the Finnish Current Care Guidelines, benzodiazepines can be used on a short-term basis to treat behavioural problems associated with Alzheimer’s disease. However, data on the benefits of these drugs in the treatment of behavioural problems is insufficient, but it is known that these drugs increase the risk of falls and cause cognitive impairment.

One of the earlier studies on Medalz study found that in Finland, benzodiazepines are used for extensive periods in persons with Alzheimer’s disease. This, together with the current finding of frequent initiations of these drugs, paints a picture of a possible delay in AD diagnoses and concerning practice of symptom-based treatment before and around diagnosis.

University of Eastern Finland www.uef.fi/en/-/bentsodiatsepiinien-ja-niiden-kaltaisten-laakkeiden-kaytto-yleistyy-alzheimerin-taudin-toteamisen-aikoihin

University of Missouri College of Engineering Dean and Bioengineering Professor Elizabeth Loboa and a team of colleagues recently discovered a way to slow and, in some cases, prevent the spread of MRSA while also regenerating new bone.

Methicillin resistant Staphylococcus aureus, or MRSA, infections are a critical problem in the medical world, including the area of regenerative medicine. This form of antibiotic-resistant staph infection can cause serious complications after typical invasive procedures and can be easily spread through skin-to-skin contact. MRSA is one of the foremost causes of osteomyelitis, a disease that inflames and destroys bone as well as surrounding soft tissue.

But University of Missouri College of Engineering Dean and Bioengineering Professor Elizabeth Loboa and a team of colleagues – Mahsa Mohiti-Asli and Casey Molina of the Joint Department of Biomedical Engineering at the University of North Carolina and North Carolina State University, Diteepeng Thamonwan of Silpakorn University in Thailand and Behnam Pourdeyhimi of NCSU – recently discovered a way to slow and, in some cases, prevent the spread of MRSA while also regenerating new bone.

Loboa and her colleagues discovered that by seeding the proper amount of silver into a biodegradable scaffold alongside bone-forming stem cells, they could still rapidly form bone while either inhibiting MRSA growth or killing the infection outright.

‘The silver ions go in and completely disrupt the MRSA cell machinery, and they can inhibit growth and kill the bacteria,’ Loboa said. ‘It’s a fine line. If you overuse too much of the silver, it’s bad for the mammalian cells. We want to make sure we don’t hurt our host cells but kill the bacterial cells.’

The threads of the bone-creating scaffold were coated with a silver ion-containing solution before testing. Silver has proven effective in undoing bacteria mechanically, making it harder for bacteria to develop immunity.

University of Missouri College of Engineering engineering.missouri.edu/2017/01/silver-ions-prove-effective-treating-killing-antibiotic-resistant-staph-infection/

Duke researchers have devised a computerized method to autonomously and quickly diagnose malaria with clinically relevant accuracy — a crucial step to successfully treating the disease and halting its spread.
In 2015 alone, malaria infected 214 million people worldwide, killing an estimated 438,000.

Malaria’s symptoms can look like many other diseases, and there are simply not enough well-trained field workers and functioning microscopes to keep pace with the parasite. While rapid diagnostic tests do exist, it is expensive to continuously purchase new tests. These tests also cannot tell how severe the infection is by tallying the number of infected cells, which is important for managing a patient’s recovery.

In a new study, engineers from Duke University report a method that uses computer deep learning’ and light-based, holographic scans to spot malaria-infected cells from a simple, untouched blood sample without any help from a human. The innovation could form the basis of a fast, reliable test that could be given by most anyone, anywhere in the field, which would be invaluable in the $2.7 billion-per-year global fight against the disease.

‘With this technique, the path is there to be able to process thousands of cells per minute,’ said Adam Wax, professor of biomedical engineering at Duke. ‘That’s a huge improvement to the 40 minutes it currently takes a field technician to stain, prepare and read a slide to personally look for infection.’
The new technique is based on a technology called quantitative phase spectroscopy. As a laser sweeps through the visible spectrum of light, sensors capture how each discrete light frequency interacts with a sample of blood. The resulting data captures a holographic image that provides a wide array of valuable information that can indicate a malarial infection.

‘We identified 23 parameters that are statistically significant for spotting malaria,’ said Han Sang Park, a doctoral student in Wax’s laboratory and first author on the paper. For example, as the disease progresses, red blood cells decrease in volume, lose haemoglobin and deform as the parasite within grows larger. This affects features such as cell volume, perimeter, shape and centre of mass.

‘However, none of the parameters were reliable more than 90 percent of the time on their own, so we decided to use them all,’ said Park.
‘To be adopted, any new diagnostic device has to be just as reliable as a trained field worker with a microscope,’ said Wax. ‘Otherwise, even with a 90 percent success rate, you’d still miss more than 20 million cases a year.’

To get a more accurate reading, Wax and Park turned to deep learning — a method by which computers teach themselves how to distinguish between different objects. By feeding data on more than 1,000 healthy and diseased cells into a computer, the deep learning program determined which sets of measurements at which thresholds most clearly distinguished healthy from diseased cells.

When they put the resulting algorithm to the test with hundreds of cells, it was able to correctly spot malaria 97 to 100 percent of the time — a number the researchers believe will increase as more cells are used to train the program. Because the technique breaks data-rich holograms down to just 23 numbers, tests can be easily transmitted in bulk, which is important for locations that often do not have reliable, fast internet connections, and that, in turn, could eliminate the need for each location to have its own computer for processing.
Wax and Park are now looking to develop the technology into a diagnostic device through a startup company called M2 Photonics Innovations. They hope to show that a device based on this technology would be accurate and cost-efficient enough to be useful in the field. Wax has also received funding to begin exploring the use of the technique for spotting cancerous cells in blood samples.

Duke University pratt.duke.edu/about/news/spotting-malaria