3D printing enables the smalles complex micro-objectives

The femtosecond laser, with pulse durations smaller than 100 femtoseconds, is being focused in a microscope into liquid photoresist which rests on a glass substrate or an optical fiber. Two photons of the red laser beam with a wavelength of 785 nm are being absorbed simultaneously in the focus and expose the photoresist. This crosslinks the polymer and hardens it. The laser beam is directed with a scanner or by moving the substrate over the substrate. After exposure, the unexposed photoresist is washed away with a solvent. Only the hardened transparent polymer remains and forms the optical element.

Using this method, optical free form surfaces can be created with sub-micrometer accuracy. The precision of the 3D laser writing allows not only for construction of common spherical lenses, but also the more ideal surfaces such as paraboloids or aspheres of higher order are possible. Particularly optical lens systems with two or more lenses can be realized for the first time with this method. This opens the door to aberration correction and microoptical imaging systems with unprecedented quality.

Full story and contact information can be found from University of Stuttgart website.

Nerve Capping Device for Treatment and Prevention of Symptomatic Neuroma CE Marked

Polyganics, a privately held medical technology company, announced that it has received the CE mark for NEUROCAP®, its nerve capping device. Polyganics intends to launch NEUROCAP® in several European countries later this year.

NEUROCAP® is an absorbable implant for the treatment and reduction of symptomatic neuroma in peripheral nerves. The device was cleared for sales in the United States in January 2016, and Polyganics introduced NEUROCAP® during the Annual Meeting of the American Society of Surgery of the Hand in Phoenix last January.

In February, the European STOP NEUROMA study started to gather evidence for the long-term effectiveness of NEUROCAP® in the reduction of painful neuroma formation. The first patients have been successfully enrolled at the MC Groep hospital in Emmeloord, The Netherlands, by Coordinating Investigator Mariëtta Bertleff, MD. Through this study, Polyganics is collecting more data on the clinical performance of NEUROCAP®’s ability to isolate the nerve end, and the product’s effectiveness with respect to the reduction of pain from the symptomatic neuroma and prevention of pain reoccurrence.

Rudy Mareel, CEO of Polyganics said, “CE regulatory approval is a key milestone for our nerve capping device. We strongly believe NEUROCAP® represents an important addition to the surgeons’ tool-box in the treatment of peripheral nerve injuries enhancing surgical outcomes and patient recovery.

Furthermore, if NEUROCAP® shows effectiveness in terms of preventing pain symptoms to return over a one-year period, the device could be used in the prevention of painful neuroma formation following amputations. This is an additional, even more significant population which is steadily increasing due to the growing prevalence of diseases such as diabetes.”

More information can be found from Polyganics website.

Researchers Show How Stem Cells Exit Bloodstream

Researchers at North Carolina State University have discovered that therapeutic stem cells exit the bloodstream in a different manner than was previously thought. This process, dubbed angiopellosis by the researchers, has implications for improving our understanding of not only intravenous stem cell therapies, but also metastatic cancers.

When white blood cells need to get to the site of an infection, they can exit the bloodstream via a process called diapedesis. In diapedesis, the white blood cell changes its shape in order to squeeze between or through the epithelial cells that form the walls of the blood vessel. Diapedesis is a well-understood process, and researchers believed that other types of cells, like therapeutic stem cells or even metastatic cancer cells, exited blood vessels in a similar way – with the cells pushing or squeezing themselves out.

But a group of researchers led by Ke Cheng, associate professor of molecular biomedical sciences at NC State with a joint appointment in the NC State/UNC-Chapel Hill Department of Biomedical Engineering, found that these stem cells behaved differently.

Therapeutic stem cells share the same ability to exit the bloodstream and target particular tissues that white blood cells do. But the precise way that they did so was not well understood, so Cheng and his team utilized a zebrafish model to study the process. The genetically modified zebrafish embryos were transparent and had fluorescently marked green blood vessels. Researchers injected the embryos with white blood cells and cardiac stem cells from humans, rats and dogs. These cells had all been marked with a red fluorescent protein.

Through time-lapse three-dimensional light sheet microscopic imaging, Cheng and his team could trace the progress of these cells as they left the blood vessel. The white blood cells exited via diapedesis, as expected. When stem cells exited the blood vessel, however, the endothelial cells lining the vessel actively expelled them. Membranes surrounding the endothelial cells on either side of the stem cell stretched themselves around the stem cell, then met in the middle to push the stem cell out of the vessel.

“When you’re talking about diapedesis, the white blood cell is active because it changes its shape in order to exit. The endothelial cells in the blood vessel are passive,” Cheng says. “But when we looked at therapeutic stem cells, we found the opposite was true – the stem cells were passive, and the endothelial cells not only changed their shape in order to surround the stem cell, they actually pushed the stem cells out of the blood vessel. We’ve named this process angiopellosis, and it represents an alternative way for cells to leave blood vessels.”

The researchers found two other key differences between angiopellosis and diapedesis: one, that angiopellosis takes hours, rather than minutes, to occur; and two, that angiopellosis allows more than one cell to exit at a time.

“Angiopellosis is really a group ticket for cells to get out of blood vessels,” Cheng says. “We observed clusters of cells passing through in this way. Obviously, this leads us to questions about whether other types of cells, like metastatic cancer cells, may be using this more effective way to exit the bloodstream, and what we may need to do to stop them.”

The research is published in Stem Cells. Tyler Allen, a graduate student in the comparative biomedical sciences program, is the first author of the paper. The research was supported by the National Institutes of Health and the American Heart Association.

More information can be found from NCSU website.

AtriCure PRO2 left atrial appendage exclusion device CE marked

AtriCure announced that it has received CE Mark for the AtriClip PRO2 Left Atrial Appendage (LAA) Exclusion System, which offers increased functionality to occlude the LAA during minimally-invasive surgical (MIS) procedures. The device was previously launched in April 2016 with FDA 510(k) Clearance in the United States.

“We are excited to bring the AtriClip PRO2 device to the European market,” said Michael Carrel, President and CEO of AtriCure. “The US launch has been well received by our customers and we’re looking forward to the continued growth of the AtriClip franchise.”

The addition of the AtriClip PRO2 device has expanded the left atrial appendage product offerings and now provides an ambidextrous locking and trigger-style clip closing mechanism, handle-based active articulation levers, and a hoopless end effector. These features have improved the ease of use and time it takes to manage the left atrial appendage.

Product information can be found from AtriCure website.

Virus nanocapsules to treat infections

Scientists at the Universitat Autònoma de Barcelona (UAB) and the Catalan Institute for Nanoscience and Nanotechnology (ICN2) have developed a nanoencapsulation system with a liposome coating in order to increase the efficacy of bacteriophages in oral phage therapy. The research demonstrated that a liposome nanoencapsulation provides the bacteriophage with greater resistance to stomach acids and increases residence time in the intestinal tract of model broiler chickens in simulated poultry farming conditions. The technology developed could be applied to bacteriophages with different morphologies to be used in phage therapy, in both animals and humans.

The efficacy of encapsulated bacteriophages has been tested with animals treated with specific bacteriophages to fight against the zoonotic bacteria Salmonella. The results demonstrated a significant reduction in the concentration of Salmonella in the intestinal tract and prolonged effects when the treatment was administered using encapsulated bacteriophages, in comparison to the effects of nonencapsulated phages.

Oral phage therapy has demonstrated to be a feasible and effective tool in the control of infections caused by different bacterial pathogens. In previous studies, the UAB Molecular Microbiology Group had published the isolation and characterisation of three virulent bacteriophages (UAB_Phi20, UAB_Phi78, and UAB_Phi87) specific to Salmonella, and demonstrated their efficacy in the reduction of the concentration of this zoonotic bacteria in models of specific pathogen-free (SPF) White Leghorn chickens, and in several experimentally contaminated food matrices. Nevertheless, in this research two limitations were observed in the use of orally administered bacteriophages: the reduced stability of the phages in extremely acid environments, such as the stomach, and short residence time in the intestinal tract.

To overcome these limitations, researchers developed a nanoencapsulation system using liposome capsules and applied them to the three aforementioned virulent bacteriophages in order to compare the effects of liposome-encapsulated phages and nonencapsulated phages on the concentration of Salmonella in model broiler chickens experimentally contaminated with the bacteria. The experiment was conducted at the UAB Farms and Experimental Fields Services, with all the conditions of a real poultry farm.

Thanks to the study, nanometric capsules were developed, with an average diameter of 320 nm and a positive charge of 33mV. The nanocapsules containing the bacteriophages were observed using a cryo-electron microscope (Cryo-TEM) and confocal microscope. Researchers observed how the liposome coating allowed the encapsulated bacteriophages to be significantly more stable in the gastric fluids. The coating also significantly improved the time the bacteriophages stayed inside the intestinal tract of the chickens. After 72 hours encapsulated bacteriophages were detected in 38.1% of animals, while only 9.5% of animals showed signs of still containing the nonencapsulated bacteriophages.

In oral therapy experiments, once the treatment was suspended, the protection provided by nonencapsulated bacteriophages disappeared, while the encapsulated ones were effective for at least another week.

The methodology developed allows encapsulating bacteriophages of different sizes and morphologies, demonstrates the advantages of using encapsulated bacteriophages for oral phage therapy and, moreover, the nanometric size allows adding it to potable water and fodder.

The research was jointly conducted by the UAB Molecular Microbiology Group from the Department of Genetics and Microbiology, directed by Montserrat Llagostera, and the Supramolecular NanoChemistry & Materials group at the ICN2, directed by ICREA professor Daniel Maspoch. The work was published recently in the journal Applied and Environmental Microbiology and is part of the PhD thesis with international mention by Joan Colom Comas entitled “Studies of the Molecular features of Three Salmonella Phages for Use in Phage Therapy and of Encapsulation Methodologies to Improve Oral Phage Administration”.

The results of this work has given way to the processing of a joint UAB and INC2 European patent.

Researchers Devise Tool to Improve Imaging of Neuronal Activity in the Brain

In a partnership melding neuroscience and electrical engineering, researchers from UNC-Chapel Hill and NC State University have developed a new technology that will allow neuroscientists to capture images of the brain almost 10 times larger than previously possible – helping them better understand the behavior of neurons in the brain.

Nervous systems are complex. After all, everything that any animal thinks or does is controlled by its nervous system. To better understand how complex nervous systems work, researchers have used an expanding array of ever more sophisticated tools that allow them to actually see what’s going on. In some cases, neuroscience researchers have had to create entirely new tools to advance their work.

This is how an electrical engineering researcher ended up co-authoring a Nature Biotechnology paper with a group of neuroscientists.

A UNC-Chapel Hill research team made up of Jeff Stirman, Ikuko Smith and Spencer Smith wanted to be able to look at “ensemble” neuronal activity related to how mice process visual input. In other words, they wanted to look at activity in neurons across multiple areas at the same time.

To do that, the researchers used a two-photon microscope, which images fluorescence. In this case, it could be used to see which neurons “light up” when active.

The problem was that conventional two-photon microscopy systems could only look at approximately one square millimeter of brain tissue at a time. That made it hard to simultaneously capture neuron activity in different areas.

This is where Michael Kudenov comes in. An assistant professor of electrical and computer engineering at NC State, Kudenov’s area of expertise is remote imaging. His work focuses on developing new instruments and sensors to improve the performance of technologies used in everything from biomedical imaging to agricultural research.

After being contacted by the UNC researchers, Kudenov designed a series of new lenses for the microscope. Stirman further refined the designs and incorporated them into an overall two-photon imaging system that allowed the researchers to scan much larger areas of the brain. Instead of capturing images covering one square millimeter of the brain, they could capture images covering more than 9.5 square millimeters.

This advance allows them to simultaneously scan widely separated populations of neurons.

As the group notes in its Nature Biotechnology paper, this work addresses “a major barrier to progress in two-photon imaging of neuronal activity: the limited field of view.”

The paper, “Wide field-of-view, multi-region, two-photon imaging of neuronal activity in the mammalian brain,” was published June 27 in the journal Nature Biotechnology.

Details can be found from NCSU website by following this link.