Category Archives: medicine

An easier and cheaper way to make: wearable and disposable medical tattoolike patches

A Sept. 29, 2015 news item on ScienceDaily features an electronic health patch that’s cheaper and easier to make,

A team of researchers has invented a method for producing inexpensive and high-performing wearable patches that can continuously monitor the body’s vital signs for human health and performance tracking. The researchers believe their new method is compatible with roll-to-roll manufacturing.

The researchers have provided a photograph of a prototype patch,

Assitant professor Nanshu Lu and her team have developed a faster, inexpensive method for making epidermal electronics. Cockrell School of Engineering

Assitant professor Nanshu Lu and her team have developed a faster, inexpensive method for making epidermal electronics. Cockrell School of Engineering

A University of Texas at Austin Sept. 29, 2015 news release (also on EurekAlert), which originated the news item, provides more details,

Led by Assistant Professor Nanshu Lu, the team’s manufacturing method aims to construct disposable tattoo-like health monitoring patches for the mass production of epidermal electronics, a popular technology that Lu helped develop in 2011.

The team’s breakthrough is a repeatable “cut-and-paste” method that cuts manufacturing time from several days to only 20 minutes. The researchers believe their new method is compatible with roll-to-roll manufacturing — an existing method for creating devices in bulk using a roll of flexible plastic and a processing machine.

Reliable, ultrathin wearable electronic devices that stick to the skin like a temporary tattoo are a relatively new innovation. These devices have the ability to pick up and transmit the human body’s vital signals, tracking heart rate, hydration level, muscle movement, temperature and brain activity.

Although it is a promising invention, a lengthy, tedious and costly production process has until now hampered these wearables’ potential.

“One of the most attractive aspects of epidermal electronics is their ability to be disposable,” Lu said. “If you can make them inexpensively, say for $1, then more people will be able to use them more frequently. This will open the door for a number of mobile medical applications and beyond.”

The UT Austin method is the first dry and portable process for producing these electronics, which, unlike the current method, does not require a clean room, wafers and other expensive resources and equipment. Instead, the technique relies on freeform manufacturing, which is similar in scope to 3-D printing but different in that material is removed instead of added.

The two-step process starts with inexpensive, pre-fabricated, industrial-quality metal deposited on polymer sheets. First, an electronic mechanical cutter is used to form patterns on the metal-polymer sheets. Second, after removing excessive areas, the electronics are printed onto any polymer adhesives, including temporary tattoo films. The cutter is programmable so the size of the patch and pattern can be easily customized.

Deji Akinwande, an associate professor and materials expert in the Cockrell School, believes Lu’s method can be transferred to roll-to-roll manufacturing.

“These initial prototype patches can be adapted to roll-to-roll manufacturing that can reduce the cost significantly for mass production,” Akinwande said. “In this light, Lu’s invention represents a major advancement for the mobile health industry.”

After producing the cut-and-pasted patches, the researchers tested them as part of their study. In each test, the researchers’ newly fabricated patches picked up body signals that were stronger than those taken by existing medical devices, including an ECG/EKG, a tool used to assess the electrical and muscular function of the heart. The team also found that their patch conforms almost perfectly to the skin, minimizing motion-induced false signals or errors.

The UT Austin wearable patches are so sensitive that Lu and her team can envision humans wearing the patches to more easily maneuver a prosthetic hand or limb using muscle signals. For now, Lu said, “We are trying to add more types of sensors including blood pressure and oxygen saturation monitors to the low-cost patch.”

Here’s a link to and a citation for the paper,

“Cut-and-Paste” Manufacture of Multiparametric Epidermal Sensor Systems by Shixuan Yang, Ying-Chen Chen, Luke Nicolini, Praveenkumar Pasupathy, Jacob Sacks, Su Becky, Russell Yang, Sanchez Daniel, Yao-Feng Chang, Pulin Wang, David Schnyer, Dean Neikirk, and Nanshu Lu. Advanced Materials DOI: 10.1002/adma.201502386 First published: 23 September 2015

This paper is behind a paywall.

Better neuroprostheses for brain diseases and mental illneses

I don’t often get news releases from Sweden but I do on occasion and, sometimes, they even come in their original Swedish versions. In this case, Lund University sent me an English language version about their latest work making brain implants (neural prostheses) safer and effective. From a Sept. 29, 2015 Lund University news release (also on EurekAlert),

Neurons thrive and grow in a new type of nanowire material developed by researchers in Nanophysics and Ophthalmology at Lund University in Sweden. In time, the results might improve both neural and retinal implants, and reduce the risk of them losing their effectiveness over time, which is currently a problem

By implanting electrodes in the brain tissue one can stimulate or capture signals from different areas of the brain. These types of brain implants, or neuro-prostheses as they are sometimes called, are used to treat Parkinson’s disease and other neurological diseases.

They are currently being tested in other areas, such as depression, severe cases of autism, obsessive-compulsive disorders and paralysis. Another research track is to determine whether retinal implants are able to replace light-sensitive cells that die in cases of Retinitis Pigmentosa and other eye diseases.

However, there are severe drawbacks associated with today’s implants. One problem is that the body interprets the implants as foreign objects, resulting in an encapsulation of the electrode, which in turn leads to loss of signal.

One of the researchers explains the approach adopted by the research team (from the news release),

“Our nanowire structure prevents the cells that usually encapsulate the electrodes – glial cells – from doing so”, says Christelle Prinz, researcher in Nanophysics at Lund University in Sweden, who developed this technique together with Maria Thereza Perez, a researcher in Ophthalmology.

“I was very pleasantly surprised by these results. In previous in-vitro experiments, the glial cells usually attach strongly to the electrodes”, she says.

To avoid this, the researchers have developed a small substrate where regions of super thin nanowires are combined with flat regions. While neurons grow and extend processes on the nanowires, the glial cells primarily occupy the flat regions in between.

“The different types of cells continue to interact. This is necessary for the neurons to survive because the glial cells provide them with important molecules.”

So far, tests have only been done with cultured cells (in vitro) but hopefully they will soon be able to continue with experiments in vivo.

The substrate is made from the semiconductor material gallium phosphide where each outgrowing nanowire has a diameter of only 80 nanometres (billionths of a metre).

Here’s a link to and a citation for the paper,

Support of Neuronal Growth Over Glial Growth and Guidance of Optic Nerve Axons by Vertical Nanowire Arrays by Gaëlle Piret, Maria-Thereza Perez, and Christelle N. Prinz. ACS Appl. Mater. Interfaces, 2015, 7 (34), pp 18944–18948 DOI: 10.1021/acsami.5b03798 Publication Date (Web): August 11, 2015

Copyright © 2015 American Chemical Society

This paper appears to be open access as I was able to link to the PDF version.

A fatigue-free stretchable conductor for foldable electronics

There’s been a lot of talk about foldable, stretchable, and/or bendable electronics, which is exciting in itself but I find this work on developing a fatigue-free conductor particularly intriguing. After all, who hasn’t purchased something that stretches, folds, etc. only to find that it becomes ‘fatigued’ and is now ‘stretched out’.

A Sept. 23, 2015 news item on Azonano describes the new conductors,

Researchers have discovered a new stretchable, transparent conductor that can be folded or stretched and released, resulting in a large curvature or a significant strain, at least 10,000 times without showing signs of fatigue.

This is a crucial step in creating a new generation of foldable electronics – think a flat-screen television that can be rolled up for easy portability – and implantable medical devices. The work, published Monday [Sept. 21, 2015] in the Proceedings of the National Academy of Sciences, pairs gold nanomesh with a stretchable substrate made with polydimethylsiloxane, or PDMS.

The research is the result of an international collaboration including the University of Houston (US), Harvard University (US), Methodist Research Institute (US), Zhengzhou University (China), Lawrence Berkeley National Laboratory (LBNL; US).

A Sept. 22, 2015 University of Houston news release by Jeannie Kever, which originated the news item, describes this -fatigue-free material in more detail,

The substrate is stretched before the gold nanomesh is placed on it – a process known as “prestretching” – and the material showed no sign of fatigue when cyclically stretched to a strain of more than 50 percent.

The gold nanomesh also proved conducive to cell growth, indicating it is a good material for implantable medical devices.

Fatigue is a common problem for researchers trying to develop a flexible, transparent conductor, making many materials that have good electrical conductivity, flexibility and transparency – all three are needed for foldable electronics – wear out too quickly to be practical, said Zhifeng Ren, a physicist at the University of Houston and principal investigator at the Texas Center for Superconductivity, who was the lead author for the paper.

The new material, produced by grain boundary lithography, solves that problem, he said.

In addition to Ren, other researchers on the project included Chuan Fei Guo and Ching-Wu “Paul” Chu, both from UH; Zhigang Suo, Qihan Liu and Yecheng Wang, all from Harvard University, and Guohui Wang and Zhengzheng Shi, both from the Houston Methodist Research Institute.

In materials science, “fatigue” is used to describe the structural damage to a material caused by repeated movement or pressure, known as “strain cycling.” Bend a material enough times, and it becomes damaged or breaks.    That means the materials aren’t durable enough for consumer electronics or biomedical devices.

“Metallic materials often exhibit high cycle fatigue, and fatigue has been a deadly disease for metals,” the researchers wrote.

“We weaken the constraint of the substrate by making the interface between the Au (gold) nanomesh and PDMS slippery, and expect the Au nanomesh to achieve superstretchability and high fatigue resistance,” they wrote in the paper. “Free of fatigue here means that both the structure and the resistance do not change or have little change after many strain cycles.”

As a result, they reported, “the Au nanomesh does not exhibit strain fatigue when it is stretched to 50 percent for 10,000 cycles.”

Many applications require a less dramatic stretch – and many materials break with far less stretching – so the combination of a sufficiently large range for stretching and the ability to avoid fatigue over thousands of cycles indicates a material that would remain productive over a long period of time, Ren said.

The grain boundary lithography involved a bilayer lift-off metallization process, which included an indium oxide mask layer and a silicon oxide sacrificial layer and offers good control over the dimensions of the mesh structure.

The researchers used mouse embryonic fibroblast cells to determine biocompatibility; that, along with the fact that the stretchability of gold nanomesh on a slippery substrate resembles the bioenvironment of tissue or organ surfaces, suggest the nanomesh “might be implanted in the body as a pacemaker electrode, a connection to nerve endings or the central nervous system, a beating heart, and so on,” they wrote.

Here’s a link to and citation for the paper,

Fatigue-free, superstretchable, transparent, and biocompatible metal electrodes by Chuan Fei Guo, Qihan Liu, Guohui Wang, Yecheng Wang, Zhengzheng Shi, Zhigang Suo, Ching-Wu Chu, and Zhifeng Ren. PNAS (Proceedings of the National Academy of Sciences)  doi: 10.1073/pnas.1516873112 Published online Sept. 21, 2015

This paper appears to be open access.

Brushing your way to nanofibres

The scientists are using what looks like a hairbrush to create nanofibres ,

Figure 2: Brush-spinning of nanofibers. (Reprinted with permission by Wiley-VCH Verlag)) [downloaded from]

Figure 2: Brush-spinning of nanofibers. (Reprinted with permission by Wiley-VCH Verlag)) [downloaded from]

A Sept. 23, 2015 Nanowerk Spotlight article by Michael Berger provides an in depth look at this technique (developed by a joint research team of scientists from the University of Georgia, Princeton University, and Oxford University) which could make producing nanofibers for use in scaffolds (tissue engineering and other applications) more easily and cheaply,

Polymer nanofibers are used in a wide range of applications such as the design of new composite materials, the fabrication of nanostructured biomimetic scaffolds for artificial bones and organs, biosensors, fuel cells or water purification systems.

“The simplest method of nanofiber fabrication is direct drawing from a polymer solution using a glass micropipette,” Alexander Tokarev, Ph.D., a Research Associate in the Nanostructured Materials Laboratory at the University of Georgia, tells Nanowerk. “This method however does not scale up and thus did not find practical applications. In our new work, we introduce a scalable method of nanofiber spinning named touch-spinning.”

James Cook in a Sept. 23, 2015 article for Materials Views provides a description of the technology,

A glass rod is glued to a rotating stage, whose diameter can be chosen over a wide range of a few centimeters to more than 1 m. A polymer solution is supplied, for example, from a needle of a syringe pump that faces the glass rod. The distance between the droplet of polymer solution and the tip of the glass rod is adjusted so that the glass rod contacts the polymer droplet as it rotates.

Following the initial “touch”, the polymer droplet forms a liquid bridge. As the stage rotates the bridge stretches and fiber length increases, with the diameter decreasing due to mass conservation. It was shown that the diameter of the fiber can be precisely controlled down to 40 nm by the speed of the stage rotation.

The method can be easily scaled-up by using a round hairbrush composed of 600 filaments.

When the rotating brush touches the surface of a polymer solution, the brush filaments draw many fibers simultaneously producing hundred kilometers of fibers in minutes.

The drawn fibers are uniform since the fiber diameter depends on only two parameters: polymer concentration and speed of drawing.

Returning to Berger’s Spotlight article, there is an important benefit with this technique,

As the team points out, one important aspect of the method is the drawing of single filament fibers.

These single filament fibers can be easily wound onto spools of different shapes and dimensions so that well aligned one-directional, orthogonal or randomly oriented fiber meshes with a well-controlled average mesh size can be fabricated using this very simple method.

“Owing to simplicity of the method, our set-up could be used in any biomedical lab and facility,” notes Tokarev. “For example, a customized scaffold by size, dimensions and othermorphologic characteristics can be fabricated using donor biomaterials.”

Berger’s and Cook’s articles offer more illustrations and details.

Here’s a link to and a citation for the paper,

Touch- and Brush-Spinning of Nanofibers by Alexander Tokarev, Darya Asheghal, Ian M. Griffiths, Oleksandr Trotsenko, Alexey Gruzd, Xin Lin, Howard A. Stone, and Sergiy Minko. Advanced Materials DOI: 10.1002/adma.201502768ViewFirst published: 23 September 2015

This paper is behind a paywall.

Repairing sensitive teeth with silica nanoparticles

Don’t rush out to talk to your dentist yet but researchers at the University of Birmingham (UK) have devised a promising technique for repairing sensitive teeth according to a Sept. 16, 2015 news item on ScienceDaily,

Researchers at the University of Birmingham have shown how the development of coated silica nanoparticles could be used in restorative treatment of sensitive teeth and preventing the onset of tooth decay.

The study, published in the Journal of Dentistry, shows how sub-micron silica particles can be prepared to deliver important compounds into damaged teeth through tubules in the dentine.

The tiny particles can be bound to compounds ranging from calcium tooth building materials to antimicrobials that prevent infection.

A Sept. 16, 2015 university of Birmingham press release (also on EurekAlert), which originated the news item, expands on the research,

Professor Damien Walmsley, from the School of Dentistry at the University of Birmingham, explained, “The dentine of our teeth have numerous microscopic holes, which are the entrances to tubules that run through to the nerve. When your outer enamel is breached, the exposure of these tubules is really noticeable. If you drink something cold, you can feel the sensitivity in your teeth because these tubules run directly through to the nerve and the soft tissue of the tooth.”

“Our plan was to use target those same tubules with a multifunctional agent that can help repair and restore the tooth, while protecting it against further infection that could penetrate the pulp and cause irreversible damage.”

The aim of restorative agents is to increase the mineral content of both the enamel and dentine, with the particles acting like seeds for further growth that would close the tubules.

Previous attempts have used compounds of calcium fluoride, combinations of carbonate-hydroxypatite nanocrystals and bioactive glass, but all have seen limited success as they are liable to aggregate on delivery to the tubules. This prevents them from being able to enter the opening which is only 1 to 4 microns in width.

However, the Birmingham team turned to sub-micron silica particles that had been prepared with a surface coating to reduce the chance of aggregation.

When observed using high definition SEM (Scanning Electron Microsopy), the researchers saw promising signs that suggested that the aggregation obstacle had been overcome.

Professor Zoe Pikramenou, from the School of Chemistry at the University of Birmingham, said, “These silica particles are available in a range of sizes, from nanometre to sub-micron, without altering their porous nature. It is this that makes them an ideal container for calcium based compounds to restore the teeth, and antibacterial compounds to protect them. All we needed to do was find the right way of coating them to get them to their target.  We have found that different coatings does change the way that they interact with the tooth surface.”

“We tested a number of different options to see which would allow for the highest level particle penetration into the tubules, and identified a hydrophobic surface coating that provides real hope for the development of an effective agent.”

Our next steps are to optimise the coatings and then see how effective the particles are blocking the communication with the inside of the tooth.  The ultimate aim is to provide relief from the pain of sensitivity.

Here’s a citation and a link to the paper,

The deposition and imaging of silica sub-micron particles in dentine by Sunil Claire, Anthony Damien Walmsley, Sophie Glinton, Hayley Floyd, Rachel Sammons, Zoe Pikramenou. Journal of Dentistry October 2015 Volume 43, Issue 10, Pages 1242–1248 DOI:
Published Online: August 07, 2015

This paper is behind a paywall.

Observing nanoparticle therapeutics interact with blood in real time

Sadly, there are no images showing nanoparticle therapeutics interacting with blood or anything else for that matter to illustrate this story but perhaps the insights offered should suffice. From Sept. 15, 2015 news item on Nanowerk,

Researchers at the National University of Singapore (NUS) have developed a technique to observe, in real time, how individual blood components interact and modify advanced nanoparticle therapeutics. The method, developed by an interdisciplinary team consisting clinician-scientist Assistant Professor Chester Lee Drum of the Department of Medicine at the NUS Yong Loo Lin School of Medicine, Professor T. Venky Venkatesan, Director of NUS Nanoscience and Nanotechnology Institute, and Assistant Professor James Kah of the Department of Biomedical Engineering at the NUS Faculty of Engineering, helps guide the design of future nanoparticles to interact in concert with human blood components, thus avoiding unwanted side effects.

A Sept. 15, 2015 NUS press release, which originated the news item, describes the research in more specific detail,

With their small size and multiple functionalities, nanoparticles have attracted intense attention as both diagnostic and drug delivery systems. However, within minutes of being delivered into the bloodstream, nanoparticles are covered with a shell of serum proteins, also known as a protein ‘corona’.

“The binding of serum proteins can profoundly change the behaviour of nanoparticles, at times leading to rapid clearance by the body and a diminished clinical outcome,” said Asst Prof Kah.

Existing methods such as mass spectroscopy and diffusional radius estimation, although useful for studying important nanoparticle parameters, are unable to provide detailed, real-time binding kinetics.

Novel method to understand nano-bio interactions

The NUS team, together with external collaborator Professor Bo Liedberg from the Nanyang Technological University, showed highly reproducible kinetics for the binding between gold nanoparticles and the four most common serum proteins: human serum albumin, fibrinogen, apolipoprotein A-1, and polyclonal IgG.

“What was remarkable about this project was the initiative taken by Abhijeet Patra, my graduate student from NUS Graduate School for Integrative Sciences and Engineering, in conceptualising the problem, and bringing together the various teams in NUS and beyond to make this a successful programme,” said Prof Venkatesan. “The key development is the use of a new technique using surface plasmon resonance (SPR) technology to measure the protein corona formed when common proteins in the bloodstream bind to nanoparticles,” he added.

The researchers first immobilised the gold nanoparticles to the surface of a SPR sensor chip with a linker molecule. The chip was specially modified with an alginate polymer layer which both provided a negative charge and active sites for ligand immobilisation, and prevented non-specific binding. Using a 6 x 6 microfluidic channel array, they studied up to 36 nanoparticle-protein interactions in a single experiment, running test samples alongside experimental controls.

“Reproducibility and reliability have been a bottleneck in the studies of protein coronas,” said Mr Abhijeet Patra. “The quality and reliability of the data depends most importantly upon the design of good control experiments. Our multiplexed SPR setup was therefore key to ensuring the reliability of our data.”

Testing different concentrations of each of the four proteins, the team found that apolipoprotein A-1 had the highest binding affinity for the gold nanoparticle surface, with an association constant almost 100 times that of the lowest affinity protein, polyclonal IgG.

“Our results show that the rate of association, rather than dissociation, is the main determinant of binding with the tested blood components,” said Asst Prof Drum.

The multiplex SPR system was also used to study the effect of modification with polyethylene (PEG), a synthetic polymer commonly used in nanoparticle formulations to prevent protein accumulation. The researchers found that shorter PEG chains (2-10 kilodaltons) are about three to four times more effective than longer PEG chains (20-30 kilodaltons) at preventing corona formation.

“The modular nature of our protocol allows us to study any nanoparticle which can be chemically tethered to the sensing surface,” explained Asst Prof Drum. “Using our technique, we can quickly evaluate a series of nanoparticle-based drug formulations before conducting in vivo studies, thereby resulting in savings in time and money and a reduction of in vivo testing,” he added.

The researchers plan to use the technology to quantitatively study protein corona formation for a variety of nanoparticle formulations, and rationally design nanomedicines for applications in cardiovascular diseases and cancer.

Here’s a link to and a citation for the paper,

Component-Specific Analysis of Plasma Protein Corona Formation on Gold Nanoparticles Using Multiplexed Surface Plasmon Resonance by Abhijeet Patra, Tao Ding, Gokce Engudar, Yi Wang, Michal Marcin Dykas, Bo Liedberg, James Chen Yong Kah, Thirumalai Venkatesan, and Chester Lee Drum. Small  DOI: 10.1002/smll.201501603 Article first published online: 10 SEP 2015

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

An easier, cheaper way to diagnose Ebola

A Sept. 9, 2015 news item on Nanotechnology Now highlights a new technology for diagnosing the Ebola virus,

A new Ebola test that uses magnetic nanoparticles could help curb the spread of the disease in western Africa. Research published in Biosensors and Bioelectronics shows that the new test is 100 times more sensitive than the current test, and easier to use. Because of this, the new test makes it easier and cheaper to diagnose cases, enabling healthcare workers to isolate patients and prevent the spread of Ebola.

The authors of the study, from the Chinese Academy of Sciences, say their new technology could be applied to the detection of any biological molecules, making it useful to diagnose other infectious diseases, like flu, and potentially detect tumors and even contamination in wastewater.

A Sept. 9, 2015 Elsevier press release, which originated the news item, provides more detail,

The Ebola virus causes an acute illness that is deadly in half of all cases, on average. The current outbreak of Ebola, which started in March 2014, affects countries in west Africa. In the most severely affected countries, like Guinea, Liberia and Sierra Leone, resources are limited, making control of the outbreak challenging. There is no vaccine for Ebola, so detecting the virus is key to controlling the outbreak: with an accurate diagnosis, patients can be isolated and treated properly, reducing the risk of spread.

“In west Africa, resources are under pressure, so complicated, expensive tests are not very helpful,” said Professor Xiyun Yan, one of the authors of the study from the Chinese Academy of Sciences. “Our new strip test is a simple, one-step test that is cheap and easy to use, and provides a visible signal, which means people don’t need training to use it. We think it will be especially helpful in rural areas, where technical equipment and skills are not available.”

Currently there are two ways to test for the Ebola virus: using a method called polymerase chain reaction (PCR), which makes copies of the molecules for detection, and with antibody-capture enzyme-linked immunosorbent assay (ELISA), which gives a visual indication when a given molecule is in a sample. PCR is very sensitive, but is expensive and complicated, requiring special skills and technical equipment. The ELISA – or gold strip test – is cheaper but sensitivity is very low, which means it often gives the wrong results.

The new test, called the nanozyme test, uses magnetic nanoparticles, which work like enzymes to make the signal stronger, giving a clearer result you can see with the naked eye. The test can detect much smaller amounts of the virus, and is 100 times more sensitive than the gold strip test.

“People have loved the strip test for many years, but it has a major weakness: it’s not sensitive enough. We’re very excited about our new nanozyme test, as it is much more sensitive and you don’t need any specialist equipment to get a quick, accurate result,” said Dr. Yan.

Strip tests work by attaching molecules called antibodies to gold particles to look for a particular molecule in a sample. When they attach to the molecule you’re looking for, in this case a virus, they produce a signal, such as a color change. In order to find the virus, the particles need to be labelled with enzymes, which speed up detection and signalling.

With the new nanozyme test, the researchers applied magnetic nanoparticles as a nanozyme probe in place of gold nanoparticles. After labeling with an antibody that attaches to the Ebola virus, this novel probe is able to recognize and separate the virus in a sample. The nanoparticles are magnetic, so to concentrate the virus particles in a sample, all you need to do is hold the sample against a magnet; no expensive equipment is needed.

The nanozyme test is 100 times more sensitive than the gold strip test, detecting molecules called glycoproteins on the surface of the Ebola virus at concentrations as low as 1 nanogram per milliliter.

The researchers have applied for a patent for the new test, which is currently being taken to west Africa by the CDC to use in the field. The researchers are also collaborating with clinical teams to apply the technology to other diseases, and with a company that treats wastewater to see if it can help remove environmental contamination.

Here’s a link to and a citation for the paper,

Nanozyme-strip for rapid local diagnosis of Ebola by Demin Duan, Kelong Fan, Dexi Zhang, Shuguang Tan, Mifang Liang, Yang Liu, Jianlin Zhang, Panhe Zhang, Wei Liu, Xiangguo Qiu, Gary P. Kobinger, George Fu Gao, Xiyun Yan. Biosensors and Bioelectronics Volume 74, 15 December 2015, Pages 134–141 doi:10.1016/j.bios.2015.05.025

This paper appears to be open access.

Faster, cheaper, pseudo-organs (also known as organoids)

There’ve been any number of ‘organoid’ stories recently, here and elsewhere. This one is special due to a quasi extra-cellular matrix (cells have a type of skeletal structure known as an extra-cellular matrix or ECM). From a Sept. 11, 2015 news item on Azonano,

Scientists have developed a new technique that produces a user friendly, low cost, tissue-engineered pseudo-organ. The chip-based model produces a faithful mimic of the in vivo liver inside a scalable fluid-handling device, demonstrating proof of principle for toxicology tests and opening up potential use in drug testing and personalised medicine.

The work was done by researchers based at the Wake Forest Institute for Regenerative Medicine and the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. They created a device architecture within which were a series of 3D liver cell constructs enclosed in a biopolymer that closely mimics the extra-cellular matrix (ECM). Surrounding the printed cells with this ECM – which the body uses to support cells in the liver – makes this model a more realistic model of the cells in vivo.

A Sept. 10, 2015 Institute of Physics (IOP) press release, which originated the news item, provides more details about the technology,

The technique uses photopatterning to produce defined 3D constructs in a microfluidic system to probe the construct quickly. “It’s basically scaled-down pluming” explains Adam Hall, an author on the paper. “This paper describes fairly hefty devices – a few mm – but we’re working to scale this down considerably.”

Collaboration proved to be the key to success; “The challenges were not too significant once Adam and I merged our areas of expertise.” adds Aleksander Skardal, another author on the paper. “With his background in devices and microfabrication, and my background in biomaterials and biofabrication, the two technologies integrated rather well.”

The 3D construct device offers a new tool in the development of drug treatments. At present, 2D testing in vitro doesn’t replicate the activity of the cells, and until now 3D systems have not provided adequate interactions of cells with the ECM, or offered particularly high-throughput testing.

This is where the combination of technologies has proven vital. “3D constructs are less effective if you can’t probe them quickly” continues Hall. “And without some important task, microfluidics are just a fun party trick.”

The researchers were also happy how quickly the techniques fell into place.

“The first time we attempted to perform the in situ photopatterning – it just worked” says Skardal. “Science isn’t always that easy, so we knew we might be onto something.”

“Yes – this was one of those rare occasions where things seemed to fall into place” adds Hall.

The researchers are now working to reduce the size of the system allowing for multiple constructs that could be tested individually. This would open potential usage in drug testing and personalised medicine.

“Imagine being able to put, for example, tumor cells from a patient on a chip and test different drug cocktails on them” they conclude. “You could determine the effectiveness and side effects of different treatments on an individual basis without endangering the patient.”

Here’s a link to and a citation for the paper,

In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device by Aleksander Skardal, Mahesh Devarasetty, Shay Soker, and Adam R Hall. Biofabrication, Volume 7, Number 3 DOI: 10.1088/1758-5090/7/3/032001 Published 11 September 2015

© 2015 IOP Publishing Ltd

This is an open access paper.

Sponges made of nanoporous gold and DNA detection

This work from the University of California at Davis seems to represent a step forward for better detection of diseases and pathogens. From a Sept. 4, 2015 news item on ScienceDaily,

Sponge-like nanoporous gold could be key to new devices to detect disease-causing agents in humans and plants, according to UC Davis researchers.

In two recent papers in Analytical Chemistry, a group from the UC Davis Department of Electrical and Computer Engineering demonstrated that they could detect nucleic acids using nanoporous gold, a novel sensor coating material, in mixtures of other biomolecules that would gum up most detectors. This method enables sensitive detection of DNA [deoxyribonucleic acid] in complex biological samples, such as serum from whole blood.

A Sept. 4, 2015 UC Davis news release on EurekAlert, which originated the news item, offers more detail,

“Nanoporous gold can be imagined as a porous metal sponge with pore sizes that are a thousand times smaller than the diameter of a human hair,” said Erkin Şeker, assistant professor of electrical and computer engineering at UC Davis and the senior author on the papers. “What happens is the debris in biological samples, such as proteins, is too large to go through those pores, but the fiber-like nucleic acids that we want to detect can actually fit through them. It’s almost like a natural sieve.”

Rapid and sensitive detection of nucleic acids plays a crucial role in early identification of pathogenic microbes and disease biomarkers. Current sensor approaches usually require nucleic acid purification that relies on multiple steps and specialized laboratory equipment, which limit the sensors’ use in the field. The researchers’ method reduces the need for purification.

“So now we hope to have largely eliminated the need for extensive sample clean-up, which makes the process conducive to use in the field,” Şeker said.

The result is a faster and more efficient process that can be applied in many settings.

The researchers hope the technology can be translated into the development of miniature point-of-care diagnostic platforms for agricultural and clinical applications.

“The applications of the sensor are quite broad ranging from detection of plant pathogens to disease biomarkers,” said Şeker.

For example, in agriculture, scientists could detect whether a certain pathogen exists on a plant without seeing any symptoms. And in sepsis cases in humans, doctors might determine bacterial contamination much more quickly than at present, preventing any unnecessary treatments.

Here are links to and citations for two recent published papers about this work,

Effect of Nanoporous Gold Thin Film Morphology on Electrochemical DNA Sensing by Pallavi Daggumati, Zimple Matharu, and Erkin Şeker. Anal. Chem., 2015, 87 (16), pp 8149–8156 DOI: 10.1021/acs.analchem.5b00846 Publication Date (Web): April 30, 2015

Copyright © 2015 American Chemical Society

Biofouling-Resilient Nanoporous Gold Electrodes for DNA Sensing by Pallavi Daggumati, Zimple Matharu, Ling Wang, and Erkin Şeker. Anal. Chem., 2015, 87 (17), pp 8618–8622 DOI: 10.1021/acs.analchem.5b02969 Publication Date (Web): August 14, 2015

Copyright © 2015 American Chemical Society

These papers are behind a paywall.

Weirdly fascinating account of malaria-carrying mosquitoes and insecticide-treated bed nets

Researchers at the Liverpool School of Tropical Medicine (LSTM) have tracked mosquitoes to observe how they interact with insecticide-laden nets. From a Sept. 1, 2015 LSTM press release (also on EurekAlert),

LSTM vector biologists Dr Philip McCall and Ms Josie Parker worked with optical engineers Prof David Towers, Dr Natalia Angarita and Dr Catherine Towers from the University of Warwick’s School of Engineering to develop infrared video tracking technology that follows individual mosquitoes in flight as they try to reach a human sleeper inside a bed net. This system allowed the scientists to measure, define and characterise in fine detail, the behavioural events and sequences of the main African malaria vector, Anopheles gambiae, as it interacts with the net. Funded as part of the €12M AvecNet research consortium, the team’s initial results are published today in the journal Nature Scientific Reports.

Dr Philip McCall, senior author on the paper, said: “Essentially, the results demonstrated that an LLIN [Long-lasting insecticidal bed net] functions as a highly efficient, fast-acting, human-baited insecticidal trap. LLINs do not repel mosquitoes – they deliver insecticide very rapidly after the briefest contact: LLIN contact of less than 1 minute per mosquito during the first ten minutes can reduce mosquito activity such that after thirty minutes, virtually no mosquitoes are still flying. Surprisingly, mosquitoes were able to detect nets of any kind while still in flight, allowing them to decelerate before they ‘collided’ with the net surface.”

The use of this innovative approach to mosquito behaviour has provided unprecedented insight into the mode of action of our most important tool for preventing malaria transmission, under conditions that are as close to natural as possible. The findings potentially could influence many aspects of mosquito control, ranging from how we test mosquito populations for insecticide resistance to the design of a next generation of LLINs. An MRC Confidence in Concept grant has funded the team to use the tracking system to explore a number of novel LLIN designs, already patented as an outcome from the current research.

The tracking system also has been deployed in a rural Tanzania, results of which will be reported shortly. The team recently was awarded £0.9M support from the Medical Research Council (MRC) for the next stage of this project, where they will use a larger three-dimensional system to track mosquitoes throughout the entire domestic environment, in experimental houses in Tanzania.

Dr McCall continued: “preliminary results in field tests indicate that these laboratory findings are consistent with behaviour of wild mosquito populations which is very encouraging. We are at the early stages of this research, but we hope that our findings, and the use of this cutting edge technology, can contribute to the development of new and advanced vector control tools that will continue to save lives in endemic countries throughout the world.”

The fascinating part follows the link to and citation for the paper,

Infrared video tracking of Anopheles gambiae at insecticide-treated bed nets reveals rapid decisive impact after brief localised net contact by Josephine E.A. Parker, Natalia Angarita-Jaimes, Mayumi Abe, Catherine E. Towers, David Towers, & Philip J. McCall. Scientific Reports 5, Article number: 13392 (2015) doi:10.1038/srep13392 Published online: 01 September 2015

This open access paper provides an explanation for why this work was undertaken,

Delivering the ‘next generation’ of LLINs or similar tools will require a thorough understanding of how LLINs function, yet remarkably little is known of the mode of action or of precisely how mosquitoes behave at the LLIN interface. Recent studies using ‘sticky-nets’ reported that host-seeking female Anopheles spp. landed preferentially on the top surface of bed nets7,8 but that lethal capture method recorded only a single landing event and no other behaviours before or after. Although clustering at the net roof is likely to be a response to an attractant ‘plume’ rising from the human beneath [emphasis mine], this too remains speculative because knowledge of mosquito flight behaviour prior to blood-feeding and of the identity and location of the key attractants that mediate the host-seeking response is limited9,10,11,12. Importantly, how insecticide treatments influence that response is unclear. Some studies reported that insecticide residues repelled mosquitoes prior to contact13,14, which would reduce or eliminate the chance of mosquitoes receiving an effective dose and potentially divert them to unprotected hosts15. Others found no evidence for such repellency16,17,18,19 indicating that LLINs attract and impact on mosquitoes by direct contact.

A further complication is the existence of what is termed ‘contact-irritancy’ or ‘excito-repellency’ [emphasis miine], whereby brief exposure to an insecticide can result in mosquitoes exhibiting avoidance behaviour, potentially before a lethal dose has been delivered13,20. Remarkably, some basic details are missing: e.g. the minimum duration of LLIN contact necessary to deliver an effective dosage is not known. Despite these phenomena being recognised for decades20,21,22, when and how they occur and their relative importance in selecting for insecticide resistance have never been fully elucidated.

Consequently, behavioural resistance [emphasis mine] to insecticides remains poorly understood and rarely reported in mosquitoes, though the risk of vector populations switching blood-feeding times, locations or host preferences in order to avoid LLINs is recognized and closely monitored today23,24,25. However, additional but less apparent or detectable behavioural changes also might exist, potentially conferring partial or complete insecticide resistance (e.g. changes in sensitivity to repellents, attractants, or modified flight or resting behaviours). In the absence of definitions or quantifications of the basic behavioural events likely to be affected26,27, these changes cannot be investigated, let alone monitored.

I am fascinated by the ‘attractant plume’, ‘excito-repellency’, and the (new to me) notion that mosquitoes can exhibit behavioural resistance.