Tag Archives: biosensors

Neurons and graphene carpets

I don’t entirely grasp the carpet analogy. Actually, I have no why they used a carpet analogy but here’s the June 12, 2018 ScienceDaily news item about the research,

A work led by SISSA [Scuola Internazionale Superiore di Studi Avanzati] and published on Nature Nanotechnology reports for the first time experimentally the phenomenon of ion ‘trapping’ by graphene carpets and its effect on the communication between neurons. The researchers have observed an increase in the activity of nerve cells grown on a single layer of graphene. Combining theoretical and experimental approaches they have shown that the phenomenon is due to the ability of the material to ‘trap’ several ions present in the surrounding environment on its surface, modulating its composition. Graphene is the thinnest bi-dimensional material available today, characterised by incredible properties of conductivity, flexibility and transparency. Although there are great expectations for its applications in the biomedical field, only very few works have analysed its interactions with neuronal tissue.

A June 12, 2018 SISSA press release (also on EurekAlert), which originated the news item, provides more detail,

A study conducted by SISSA – Scuola Internazionale Superiore di Studi Avanzati, in association with the University of Antwerp (Belgium), the University of Trieste and the Institute of Science and Technology of Barcelona (Spain), has analysed the behaviour of neurons grown on a single layer of graphene, observing a strengthening in their activity. Through theoretical and experimental approaches the researchers have shown that such behaviour is due to reduced ion mobility, in particular of potassium, to the neuron-graphene interface. This phenomenon is commonly called ‘ion trapping’, already known at theoretical level, but observed experimentally for the first time only now. “It is as if graphene behaves as an ultra-thin magnet on whose surface some of the potassium ions present in the extra cellular solution between the cells and the graphene remain trapped. It is this small variation that determines the increase in neuronal excitability” comments Denis Scaini, researcher at SISSA who has led the research alongside Laura Ballerini.

The study has also shown that this strengthening occurs when the graphene itself is supported by an insulator, like glass, or suspended in solution, while it disappears when lying on a conductor. “Graphene is a highly conductive material which could potentially be used to coat any surface. Understanding how its behaviour varies according to the substratum on which it is laid is essential for its future applications, above all in the neurological field” continues Scaini, “considering the unique properties of graphene it is natural to think for example about the development of innovative electrodes of cerebral stimulation or visual devices”.

It is a study with a double outcome. Laura Ballerini comments as follows: “This ‘ion trap’ effect was described only in theory. Studying the impact of the ‘technology of materials’ on biological systems, we have documented a mechanism to regulate membrane excitability, but at the same time we have also experimentally described a property of the material through the biology of neurons.”

Dexter Johnson in a June 13, 2018 posting, on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website), provides more context for the work (Note: Links have been removed),

While graphene has been tapped to deliver on everything from electronics to optoelectronics, it’s a bit harder to picture how it may offer a key tool for addressing neurological damage and disorders. But that’s exactly what researchers have been looking at lately because of the wonder material’s conductivity and transparency.

In the most recent development, a team from Europe has offered a deeper understanding of how graphene can be combined with neurological tissue and, in so doing, may have not only given us an additional tool for neurological medicine, but also provided a tool for gaining insights into other biological processes.

“The results demonstrate that, depending on how the interface with [single-layer graphene] is engineered, the material may tune neuronal activities by altering the ion mobility, in particular potassium, at the cell/substrate interface,” said Laura Ballerini, a researcher in neurons and nanomaterials at SISSA.

Ballerini provided some context for this most recent development by explaining that graphene-based nanomaterials have come to represent potential tools in neurology and neurosurgery.

“These materials are increasingly engineered as components of a variety of applications such as biosensors, interfaces, or drug-delivery platforms,” said Ballerini. “In particular, in neural electrode or interfaces, a precise requirement is the stable device/neuronal electrical coupling, which requires governing the interactions between the electrode surface and the cell membrane.”

This neuro-electrode hybrid is at the core of numerous studies, she explained, and graphene, thanks to its electrical properties, transparency, and flexibility represents an ideal material candidate.

In all of this work, the real challenge has been to investigate the ability of a single atomic layer to tune neuronal excitability and to demonstrate unequivocally that graphene selectively modifies membrane-associated neuronal functions.

I encourage you to read Dexter’s posting as it clarifies the work described in the SISSA press release for those of us (me) who may fail to grasp the implications.

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

Single-layer graphene modulates neuronal communication and augments membrane ion currents by Niccolò Paolo Pampaloni, Martin Lottner, Michele Giugliano, Alessia Matruglio, Francesco D’Amico, Maurizio Prato, Josè Antonio Garrido, Laura Ballerini, & Denis Scaini. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0163-6 Published online June 13, 2018

This paper is behind a paywall.

All this brings to mind a prediction made about the Graphene Flagship and the Human Brain Project shortly after the European Commission announced in January 2013 that each project had won funding of 1B Euros to be paid out over a period of 10 years. The prediction was that scientists would work on graphene/human brain research.

Create gold nanoparticles and nanowires with water droplets.

For some reason it took a lot longer than usual to find this research paper despite having the journal (Nature Communications), the title (Spontaneous formation …), and the authors’ names. Thankfully, success was wrested from the jaws of defeat (I don’t care if that is trite; it’s how I felt) and links, etc. follow at the end as usual.

An April 19, 2018 Stanford University news release (also on EurekAlert) spins fascinating tale,

An experiment that, by design, was not supposed to turn up anything of note instead produced a “bewildering” surprise, according to the Stanford scientists who made the discovery: a new way of creating gold nanoparticles and nanowires using water droplets.

The technique, detailed April 19 [2018] in the journal Nature Communications, is the latest discovery in the new field of on-droplet chemistry and could lead to more environmentally friendly ways to produce nanoparticles of gold and other metals, said study leader Richard Zare, a chemist in the School of Humanities and Sciences and a co-founder of Stanford Bio-X.

“Being able to do reactions in water means you don’t have to worry about contamination. It’s green chemistry,” said Zare, who is the Marguerite Blake Wilbur Professor in Natural Science at Stanford.

Noble metal

Gold is known as a noble metal because it is relatively unreactive. Unlike base metals such as nickel and copper, gold is resistant to corrosion and oxidation, which is one reason it is such a popular metal for jewelry.

Around the mid-1980s, however, scientists discovered that gold’s chemical aloofness only manifests at large, or macroscopic, scales. At the nanometer scale, gold particles are very chemically reactive and make excellent catalysts. Today, gold nanostructures have found a role in a wide variety of applications, including bio-imaging, drug delivery, toxic gas detection and biosensors.

Until now, however, the only reliable way to make gold nanoparticles was to combine the gold precursor chloroauric acid with a reducing agent such as sodium borohydride.

The reaction transfers electrons from the reducing agent to the chloroauric acid, liberating gold atoms in the process. Depending on how the gold atoms then clump together, they can form nano-size beads, wires, rods, prisms and more.

A spritz of gold

Recently, Zare and his colleagues wondered whether this gold-producing reaction would proceed any differently with tiny, micron-size droplets of chloroauric acid and sodium borohydide. How large is a microdroplet? “It is like squeezing a perfume bottle and out spritzes a mist of microdroplets,” Zare said.

From previous experiments, the scientists knew that some chemical reactions proceed much faster in microdroplets than in larger solution volumes.

Indeed, the team observed that gold nanoparticle grew over 100,000 times faster in microdroplets. However, the most striking observation came while running a control experiment in which they replaced the reducing agent – which ordinarily releases the gold particles – with microdroplets of water.

“Much to our bewilderment, we found that gold nanostructures could be made without any added reducing agents,” said study first author Jae Kyoo Lee, a research associate.

Viewed under an electron microscope, the gold nanoparticles and nanowires appear fused together like berry clusters on a branch.

The surprise finding means that pure water microdroplets can serve as microreactors for the production of gold nanostructures. “This is yet more evidence that reactions in water droplets can be fundamentally different from those in bulk water,” said study coauthor Devleena Samanta, a former graduate student in Zare’s lab and co-author on the paper.

If the process can be scaled up, it could eliminate the need for potentially toxic reducing agents that have harmful health side effects or that can pollute waterways, Zare said.

It’s still unclear why water microdroplets are able to replace a reducing agent in this reaction. One possibility is that transforming the water into microdroplets greatly increases its surface area, creating the opportunity for a strong electric field to form at the air-water interface, which may promote the formation of gold nanoparticles and nanowires.

“The surface area atop a one-liter beaker of water is less than one square meter. But if you turn the water in that beaker into microdroplets, you will get about 3,000 square meters of surface area – about the size of half a football field,” Zare said.

The team is exploring ways to utilize the nanostructures for various catalytic and biomedical applications and to refine their technique to create gold films.

“We observed a network of nanowires that may allow the formation of a thin layer of nanowires,” Samanta said.

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

Spontaneous formation of gold nanostructures in aqueous microdroplets by Jae Kyoo Lee, Devleena Samanta, Hong Gil Nam, & Richard N. Zare. Nature Communicationsvolume 9, Article number: 1562 (2018) doi:10.1038/s41467-018-04023-z Published online: 19 April 2018

Not unsurprisingly given Zare’s history as recounted in the news release, this paper is open access.

Using melanin in bioelectronic devices

Brazilian researchers are working with melanin to make biosensors and other bioelectronic devices according to a Dec. 20, 2016 news item on phys.org,

Bioelectronics, sometimes called the next medical frontier, is a research field that combines electronics and biology to develop miniaturized implantable devices capable of altering and controlling electrical signals in the human body. Large corporations are increasingly interested: a joint venture in the field has recently been announced by Alphabet, Google’s parent company, and pharmaceutical giant GlaxoSmithKline (GSK).

One of the challenges that scientists face in developing bioelectronic devices is identifying and finding ways to use materials that conduct not only electrons but also ions, as most communication and other processes in the human organism use ionic biosignals (e.g., neurotransmitters). In addition, the materials must be biocompatible.

Resolving this challenge is one of the motivations for researchers at São Paulo State University’s School of Sciences (FC-UNESP) at Bauru in Brazil. They have succeeded in developing a novel route to more rapidly synthesize and to enable the use of melanin, a polymeric compound that pigments the skin, eyes and hair of mammals and is considered one of the most promising materials for use in miniaturized implantable devices such as biosensors.

A Dec. 14, 2016 FAPESP (São Paulo Research Foundation) press release, which originated the news item, further describes both the research and a recent meeting where the research was shared (Note: A link has been removed),

Some of the group’s research findings were presented at FAPESP Week Montevideo during a round-table session on materials science and engineering.

The symposium was organized by the Montevideo Group Association of Universities (AUGM), Uruguay’s University of the Republic (UdelaR) and FAPESP and took place on November 17-18 at UdelaR’s campus in Montevideo. Its purpose was to strengthen existing collaborations and establish new partnerships among South American scientists in a range of knowledge areas. Researchers and leaders of institutions in Uruguay, Brazil, Argentina, Chile and Paraguay attended the meeting.

“All the materials that have been tested to date for applications in bioelectronics are entirely synthetic,” said Carlos Frederico de Oliveira Graeff, a professor at UNESP Bauru and principal investigator for the project, in an interview given to Agência FAPESP.

“One of the great advantages of melanin is that it’s a totally natural compound and biocompatible with the human body: hence its potential use in electronic devices that interface with brain neurons, for example.”

Application challenges

According to Graeff, the challenges of using melanin as a material for the development of bioelectronic devices include the fact that like other carbon-based materials, such as graphene, melanin is not easily dispersible in an aqueous medium, a characteristic that hinders its application in thin-film production.

Furthermore, the conventional process for synthesizing melanin is complex: several steps are hard to control, it can last up to 56 days, and it can result in disorderly structures.

In a series of studies performed in recent years at the Center for Research and Development of Functional Materials (CDFM), where Graeff is a leading researcher and which is one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP, he and his collaborators managed to obtain biosynthetic melanin with good dispersion in water and a strong resemblance to natural melanin using a novel synthesis route.

The process developed by the group at CDMF takes only a few hours and is based on changes in parameters such as temperature and the application of oxygen pressure to promote oxidation of the material.

By applying oxygen pressure, the researchers were able to increase the density of carboxyl groups, which are organic functional groups consisting of a carbon atom double bonded to an oxygen atom and single bonded to a hydroxyl group (oxygen + hydrogen). This enhances solubility and facilitates the suspension of biosynthetic melanin in water.

“The production of thin films of melanin with high homogeneity and quality is made far easier by these characteristics,” Graeff said.

By increasing the density of carboxyl groups, the researchers were also able to make biosynthetic melanin more similar to the biological compound.

In living organisms, an enzyme that participates in the synthesis of melanin facilitates the production of carboxylic acids. The new melanin synthesis route enabled the researchers to mimic the role of this enzyme chemically while increasing carboxyl group density.

“We’ve succeeded in obtaining a material that’s very close to biological melanin by chemical synthesis and in producing high-quality film for use in bioelectronic devices,” Graeff said.

Through collaboration with colleagues at research institutions in Canada [emphasis mine], the Brazilian researchers have begun using the material in a series of applications, including electrical contacts, pH sensors and photovoltaic cells.

More recently, they have embarked on an attempt to develop a transistor, a semiconductor device used to amplify or switch electronic signals and electrical power.

“Above all, we aim to produce transistors precisely in order to enhance this coupling of electronics with biological systems,” Graeff said.

I’m glad to have gotten some information about the work in South America. It’s one of FrogHeart’s shortcomings that I have so little about the research in that area of the world. I believe this is largely due to my lack of Spanish language skills. Perhaps one day there’ll be a universal translator that works well. In the meantime, it was a surprise to see Canada mentioned in this piece. I wonder which Canadian research institutions are involved with this research in South America.

Wearable microscopes

It never occurred to me that someone might want a wearable microscope but, apparently, there is a need. A Sept. 27, 2016 news item on phys.org,

UCLA [University of California at Los Angeles] researchers working with a team at Verily Life Sciences have designed a mobile microscope that can detect and monitor fluorescent biomarkers inside the skin with a high level of sensitivity, an important tool in tracking various biochemical reactions for medical diagnostics and therapy.

A Sept. 26, 2016 UCLA news release by Meghan Steele Horan, which originated the news item, describes the work in more detail,

This new system weighs less than a one-tenth of a pound, making it small and light enough for a person to wear around their bicep, among other parts of their body. In the future, technology like this could be used for continuous patient monitoring at home or at point-of-care settings.

The research, which was published in the journal ACS Nano, was led by Aydogan Ozcan, UCLA’s Chancellor’s Professor of Electrical Engineering and Bioengineering and associate director of the California NanoSystems Institute and Vasiliki Demas of Verily Life Sciences (formerly Google Life Sciences).

Fluorescent biomarkers are routinely used for cancer detection and drug delivery and release among other medical therapies. Recently, biocompatible fluorescent dyes have emerged, creating new opportunities for noninvasive sensing and measuring of biomarkers through the skin.

However, detecting artificially added fluorescent objects under the skin is challenging. Collagen, melanin and other biological structures emit natural light in a process called autofluorescence. Various methods have been tried to investigate this problem using different sensing systems. Most are quite expensive and difficult to make small and cost-effective enough to be used in a wearable imaging system.

To test the mobile microscope, researchers first designed a tissue phantom — an artificially created material that mimics human skin optical properties, such as autofluorescence, absorption and scattering. The target fluorescent dye solution was injected into a micro-well with a volume of about one-hundredth of a microliter, thinner than a human hair, and subsequently implanted into the tissue phantom half a millimeter to 2 millimeters from the surface — which would be deep enough to reach blood and other tissue fluids in practice.

To measure the fluorescent dye, the wearable microscope created by Ozcan and his team used a laser to hit the skin at an angle. The fluorescent image at the surface of the skin was captured via the wearable microscope. The image was then uploaded to a computer where it was processed using a custom-designed algorithm, digitally separating the target fluorescent signal from the autofluorescence of the skin, at a very sensitive parts-per-billion level of detection.

“We can place various tiny bio-sensors inside the skin next to each other, and through our imaging system, we can tell them apart,” Ozcan said. “We can monitor all these embedded sensors inside the skin in parallel, even understand potential misalignments of the wearable imager and correct it to continuously quantify a panel of biomarkers.”

This computational imaging framework might also be used in the future to continuously monitor various chronic diseases through the skin using an implantable or injectable fluorescent dye.

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

Quantitative Fluorescence Sensing Through Highly Autofluorescent, Scattering, and Absorbing Media Using Mobile Microscopy by Zoltán Göröcs, Yair Rivenson, Hatice Ceylan Koydemir, Derek Tseng, Tamara L. Troy, Vasiliki Demas, and Aydogan Ozcan. ACS Nano, 2016, 10 (9), pp 8989–8999 DOI: 10.1021/acsnano.6b05129 Publication Date (Web): September 13, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

Tiny sensors produced by nanoscale 3D printing could lead to new generation of atomic force microscopes

A Sept. 26, 2016 news item on Nanowerk features research into producing smaller sensors for atomic force microscopes (AFMs) to achieve greater sensitivity,

Tiny sensors made through nanoscale 3D printing may be the basis for the next generation of atomic force microscopes. These nanosensors can enhance the microscopes’ sensitivity and detection speed by miniaturizing their detection component up to 100 times. The sensors were used in a real-world application for the first time at EPFL, and the results are published in Nature Communications.

A Sept. 26, 2016 École Polytechnique Fédérale de Lausanne (EPFL; Switzerland) press release by Laure-Anne Pessina, which originated the news item, expands on the theme (Note: A link has been removed),

Atomic force microscopy is based on powerful technology that works a little like a miniature turntable. A tiny cantilever with a nanometric tip passes over a sample and traces its relief, atom by atom. The tip’s infinitesimal up-and-down movements are picked up by a sensor so that the sample’s topography can be determined. (…)

One way to improve atomic force microscopes is to miniaturize the cantilever, as this will reduce inertia, increase sensitivity, and speed up detection. Researchers at EPFL’s Laboratory for Bio- and Nano-Instrumentation achieved this by equipping the cantilever with a 5-nanometer thick sensor made with a nanoscale 3D-printing technique. “Using our method, the cantilever can be 100 times smaller,” says Georg Fantner, the lab’s director.

Electrons that jump over obstacles

The nanometric tip’s up-and-down movements can be measured through the deformation of the sensor placed at the fixed end of the cantilever. But because the researchers were dealing with minute movements – smaller than an atom – they had to pull a trick out of their hat.

Together with Michael Huth’s lab at Goethe Universität at Frankfurt am Main, they developed a sensor made up of highly conductive platinum nanoparticles surrounded by an insulating carbon matrix. Under normal conditions, the carbon isolates the electrons. But at the nano-scale, a quantum effect comes into play: some electrons jump through the insulating material and travel from one nanoparticle to the next. “It’s sort of like if people walking on a path came up against a wall and only the courageous few managed to climb over it,” said Fantner.

When the shape of the sensor changes, the nanoparticles move further away from each other and the electrons jump between them less frequently. Changes in the current thus reveal the deformation of the sensor and the composition of the sample.

Tailor-made sensors

The researchers’ real feat was in finding a way to produce these sensors in nanoscale dimensions while carefully controlling their structure and, by extension, their properties. “In a vacuum, we distribute a precursor gas containing platinum and carbon atoms over a substrate. Then we apply an electron beam. The platinum atoms gather and form nanoparticles, and the carbon atoms naturally form a matrix around them,” said Maja Dukic, the article’s lead author. “By repeating this process, we can build sensors with any thickness and shape we want. We have proven that we could build these sensors and that they work on existing infrastructures. Our technique can now be used for broader applications, ranging from biosensors, ABS sensors for cars, to touch sensors on flexible membranes in prosthetics and artificial skin.”

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

Direct-write nanoscale printing of nanogranular tunnelling strain sensors for sub-micrometre cantilevers by Maja Dukic, Marcel Winhold, Christian H. Schwalb, Jonathan D. Adams, Vladimir Stavrov, Michael Huth, & Georg E. Fantner. Nature Communications 7, Article number: 12487 doi:10.1038/ncomms12487 Published  26 September 2016

This is an open access paper.

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 http://www.nanowerk.com/spotlight/spotid=41398.php]

Figure 2: Brush-spinning of nanofibers. (Reprinted with permission by Wiley-VCH Verlag)) [downloaded from http://www.nanowerk.com/spotlight/spotid=41398.php]

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.

Carbon nanotubes as sensors in the body

Rachel Ehrenberg has written an Aug. 21, 2015 news item about the latest and greatest carbon nanotube-based biomedical sensors for the journal Nature,

The future of medical sensors may be going down the tubes. Chemists are developing tiny devices made from carbon nanotubes wrapped with polymers to detect biologically important compounds such as insulin, nitric oxide and the blood-clotting protein fibrinogen. The hope is that these sensors could simplify and automate diagnostic tests.

Preliminary experiments in mice, reported by scientists at a meeting of the American Chemical Society in Boston, Massachusetts, this week [Aug. 16 – 20, 2015], suggest that the devices are safe to introduce into the bloodstream or implant under the skin. Researchers also presented data showing that the nanotube–polymer complexes could measure levels of large molecules, a feat that has been difficult for existing technologies.

Ehrenberg focuses on one laboratory in particular (Note: Links have been removed),

“Anything the body makes, it is meant to degrade,” says chemical engineer Michael Strano, whose lab at the Massachusetts Institute of Technology (MIT) in Cambridge is behind much of the latest work1. “Our vision is to make a sensing platform that can monitor a whole range of molecules, and do it in the long term.”

To design one sensor, MIT  researchers coated nanotubes with a mix of polymers and nucleotides and screened for configurations that would bind to the protein fibrinogen. This large molecule is important for building blood clots; its concentration can indicate bleeding disorders, liver disease or impending cardiovascular trouble. The team recently hit on a material that worked — a first for such a large molecule, according to MIT nanotechnology specialist Gili Bisker. Bisker said at the chemistry meeting that the fibrinogen-detecting nanotubes could be used to measure levels of the protein in blood samples, or implanted in body tissue to detect changing fibrinogen levels that might indicate a clot.

The MIT team has also developed2 a sensor that can be inserted beneath the skin to monitor glucose or insulin levels in real time, Bisker reported. The team imagines putting a small patch that contains a wireless device on the skin just above the embedded sensor. The patch would shine light on the sensor and measure its fluorescence, then transmit that data to a mobile phone for real-time monitoring.

Another version of the sensor, developed3 at MIT by biomedical engineer Nicole Iverson and colleagues, detects nitric oxide. This signalling molecule typically indicates inflammation and is associated with many cancer cells. When embedded in a hydrogel matrix, the sensor kept working in mice for more than 400 days and caused no local inflammation, MIT chemical engineer Michael Lee reported. The nitric oxide sensors also performed well when injected into the bloodstreams of mice, successfully passing through small capillaries in the lungs, which are an area of concern for nanotube toxicity. …

There’s at least one corporate laboratory (Google X), working on biosensors although their focus is a little different. From a Jan. 9, 2015 article by Brian Womack and Anna Edney for BloombergBusiness,

Google Inc. sent employees with ties to its secretive X research group to meet with U.S. regulators who oversee medical devices, raising the possibility of a new product that may involve biosensors from the unit that developed computerized glasses.

The meeting included at least four Google workers, some of whom have connections with Google X — and have done research on sensors, including contact lenses that help wearers monitor their biological data. Google staff met with those at the Food and Drug Administration who regulate eye devices and diagnostics for heart conditions, according to the agency’s public calendar. [emphasis mine]

This approach from Google is considered noninvasive,

“There is actually one interface on the surface of the body that can literally provide us with a window of what happens inside, and that’s the surface of the eye,” Parviz [Babak Parviz, … was involved in the Google Glass project and has talked about putting displays on contact lenses, including lenses that monitor wearer’s health]  said in a video posted on YouTube. “It’s a very interesting chemical interface.”

Of course, the assumption is that all this monitoring is going to result in  healthier people but I can’t help thinking about an old saying ‘a little knowledge can be a dangerous thing’. For example, we lived in a world where bacteria roamed free and then we learned how to make them visible, determined they were disease-causing, and began campaigns for killing them off. Now, it turns out that at least some bacteria are good for us and, moreover, we’ve created other, more dangerous bacteria that are drug-resistant. Based on the bacteria example, is it possible that with these biosensors we will observe new phenomena and make similar mistakes?

Nanocellulose as a biosensor

While nanocellulose always makes my antennae quiver (for anyone unfamiliar with the phrase, it means something along the lines of ‘attracts my attention’), it’s the collaboration which intrigues me most about this research. From a July 23, 2015 news item on Azonano (Note: A link has been removed),

An international team led by the ICREA Prof Arben Merkoçi has just developed new sensing platforms based on bacterial cellulose nanopaper. These novel platforms are simple, low cost and easy to produce and present outstanding properties that make them ideal for optical (bio)sensing applications. …

ICN2 [Catalan Institute of Nanoscience and Nanotechnology; Spain] researchers are going a step further in the development of simple, low cost and easy to produce biosensors. In an article published in ACS Nano they recently reported various innovative nanopaper-based optical sensing platforms. To achieve this endeavour the corresponding author ICREA Prof Arben Merkoçi, Group Leader at ICN2 and the first author, Dr Eden Morales-Narváez (from ICN2) and Hamed Golmohammadi (visiting researcher at ICN2), established an international collaboration with the Shahid Chamran University (Iran), the Gorgan University of Agricultural Sciences and Natural Resources (Iran) and the Academy of Sciences of the Czech Republic. [emphases mine]

Spain, Iran, and the Czech Republic. That’s an interesting combination of countries.

A July 23, 2015 ICN2 press release, which originated the news item, provides more explanations and detail,

Cellulose is simple, naturally abundant and low cost. However, cellulose fibres ranging at the nanoscale exhibit extraordinary properties such as flexibility, high crystallinity, biodegradability and optical transparency, among others. The nanomaterial can be extracted from plant cellulose pulp or synthetized by non-pathogenic bacteria. Currently, nanocellulose is under active research to develop a myriad of applications including filtration, wound dressing, pollution removal approaches or flexible and transparent electronics, whereas it has been scarcely explored for optical (bio)sensing applications.

The research team led by ICREA Prof Arben Merkoçi seeks to design, fabricate, and test simple, disposable and versatile sensing platforms based on this material. They designed different bacterial cellulose nanopaper based optical sensing platforms. In the article, the authors describe how the material can be tuned to exhibit plasmonic or photoluminescent properties that can be exploited for sensing applications. Specifically, they have prepared two types of plasmonic nanopaper and two types of photoluminescent nanopaper using different optically active nanomaterials.

The researchers took advantage of the optical transparency, porosity, hydrophilicity, and amenability to chemical modification of the material. The bacterial cellulose employed throughout this research was obtained using a bottom-up approach and it is shown that it can be easily turned into useful devices for sensing applications using wax printing or simple punch tools. The scientific team also demonstrates how these novel sensing platforms can be modulated to detect biologically relevant analytes such as cyanide and pathogens among others.

According to the authors, this class of platforms will prove valuable for displaying analytical information in diverse fields such as diagnostics, environmental monitoring and food safety. Moreover, since bacterial cellulose is flexible, lightweight, biocompatible and biodegradable, the proposed composites could be used as wearable optical sensors and could even be integrated into novel theranostic devices. In general, paper-based sensors are known to be simple, portable, disposable, low power-consuming and inexpensive devices that might be exploited in medicine, detection of explosives or hazardous compounds and environmental studies.

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

Nanopaper as an Optical Sensing Platform by Eden Morales-Narváez, Hamed Golmohammadi, Tina Naghdi, Hossein Yousefi, Uliana Kostiv, Daniel Horák, Nahid Pourreza, and Arben Merkoçi.ACS Nano, Article ASAP DOI: 10.1021/acsnano.5b03097 Publication Date (Web): July 2, 2015
Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Do-it-yourself sensors possible with biocatalytic pen technology

The engineers at the University of California at San Diego (UCSD) are envisioning a future where anyone can create a biosensor anywhere. From a March 3, 2015 news item on Azonano,

A new simple tool developed by nanoengineers at the University of California, San Diego, is opening the door to an era when anyone will be able to build sensors, anywhere, including physicians in the clinic, patients in their home and soldiers in the field.

The team from the University of California, San Diego, developed high-tech bio-inks that react with several chemicals, including glucose. They filled off-the-shelf ballpoint pens with the inks and were able to draw sensors to measure glucose directly on the skin and sensors to measure pollution on leaves.

A March 2, 2015 UCSD news release by Ioana Patringenaru, which originated the news item, describes the researchers’ hopes for this technology,

Skin and leaves aren’t the only media on which the pens could be used. Researchers envision sensors drawn directly on smart phones for personalized and inexpensive health monitoring or on external building walls for monitoring of toxic gas pollutants. The sensors also could be used on the battlefield to detect explosives and nerve agents.

The team, led by Joseph Wang, the chairman of the Department of NanoEngineering at the University of California, San Diego, published their findings in the Feb. 26 [2015] issue of Advanced Healthcare Materials. Wang also directs the Center for Wearable Sensors at UC San Diego.

“Our new biocatalytic pen technology, based on novel enzymatic inks, holds considerable promise for a broad range of applications on site and in the field,” Wang said.

The news release goes on to describe one of the key concerns with developing the ink,

The biggest challenge the researchers faced was making inks from chemicals and biochemicals that aren’t harmful to humans or plants; could function as the sensors’ electrodes; and retain their properties over long periods in storage and in various conditions. Researchers turned to biocompatible polyethylene glycol, which is used in several drug delivery applications, as a binder. To make the inks conductive to electric current they used graphite powder. They also added chitosan, an antibacterial agent which is used in bandages to reduce bleeding, to make sure the ink adhered to any surfaces it was used on. The inks’ recipe also includes xylitol, a sugar substitute, which helps stabilize enzymes that react with several chemicals the do-it-yourself sensors are designed to monitor.

There’s a backstory to this research,

Wang’s team has been investigating how to make glucose testing for diabetics easier for several years. The same team of engineers recently developed non-invasive glucose sensors in the form of temporary tattoos. In this study, they used pens, loaded with an ink that reacts to glucose, to draw reusable glucose-measuring sensors on a pattern printed on a transparent, flexible material which includes an electrode. Researchers then pricked a subject’s finger and put the blood sample on the sensor. The enzymatic ink reacted with glucose and the electrode recorded the measurement, which was transmitted to a glucose-measuring device. Researchers then wiped the pattern clean and drew on it again to take another measurement after the subject had eaten.

Researchers estimate that one pen contains enough ink to draw the equivalent of 500 high-fidelity glucose sensor strips. Nanoengineers also demonstrated that the sensors could be drawn directly on the skin and that they could communicate with a Bluetooth-enabled electronic device that controls electrodes called a potentiostat, to gather data.

As mentioned earlier, there are more applications being considered (from the news release),

The pens would also allow users to draw sensors that detect pollutants and potentially harmful chemicals sensors on the spot. Researchers demonstrated that this was possible by drawing a sensor on a leaf with an ink loaded with enzymes that react with phenol, an industrial chemical, which can also be found in cosmetics, including sunscreen. The leaf was then dipped in a solution of water and phenol and the sensor was connected to a pollution detector. The sensors could be modified to react with many pollutants, including heavy metals or pesticides.

Next steps include connecting the sensors wirelessly to monitoring devices and investigating how the sensors perform in difficult conditions, including extreme temperatures, varying humidity and extended exposure to sunlight.

The researchers’ have provided a picture of the pen and a leaf,

Researchers drew sensors capable of detecting pollutants on a leaf. Courtesy: University of California at San Diego

Researchers drew sensors capable of detecting pollutants on a leaf. Courtesy: University of California at San Diego

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

Biocompatible Enzymatic Roller Pens for Direct Writing of Biocatalytic Materials: “Do-it-Yourself” Electrochemical Biosensors by Amay J. Bandodkar, Wenzhao Jia, Julian Ramírez, and Joseph Wang. Advanced Healthcare Materials DOI: 10.1002/adhm.201400808 Article first published online: 26 FEB 2015

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

This article is behind a paywall.

Monitoring health with graphene rubber bands

An Aug. 20, 2014 news item on Azonano highlights graphene research from the University of Surrey (UK) and Trinity College Dublin (Ireland),

Although body motion sensors already exist in different forms, they have not been widely used due to their complexity and cost of production.

Now researchers from the University of Surrey and Trinity College Dublin have for the first time treated common elastic bands with graphene, to create a flexible sensor that is sensitive enough for medical use and can be made cheaply.

An Aug. 15, 2014 University of Surrey press release (also on EurekAlert), which originated the news item, describes the innovation (Note: A link has been removed),

Once treated, the rubber bands remain highly pliable. By fusing this material with graphene – which imparts an electromechanical response on movement – the material can be used as a sensor to measure a patient’s breathing, heart rate or movement, alerting doctors to any irregularities.

“Until now, no such sensor has been produced that meets these needs,” said Surrey’s Dr Alan Dalton. “It sounds like a simple concept, but our graphene-infused rubber bands could really help to revolutionise remote healthcare – and they’re very cheap to manufacture.”

“These sensors are extraordinarily cheap compared to existing technologies. Each device would probably cost pennies instead of pounds, making it ideal technology for use in developing countries where there are not enough medically trained staff to effectively monitor and treat patients quickly.” [commented corresponding author, Professor Jonathan Coleman from Trinity College, Dublin]

Trinity College Dublin issued an Aug. 20, 2014 press release, which provides a little more technical detail and clarifies who led the team for anyone who may been curious about the matter,

The team – led by Professor of Chemical Physics at Trinity, Jonathan Coleman, one of the world’s leading nanoscientists – infused rubber bands with graphene, a nano-material derived from pencil lead which is 10,000 times smaller than the width of a human hair. This process is simple and compatible with normal manufacturing techniques. While rubber does not normally conduct electricity, the addition of graphene made the rubber bands electrically conductive without degrading the mechanical properties of the rubber. Tests showed that any electrical current flowing through the graphene-infused rubber bands was very strongly affected if the band was stretched. As a result, if the band is attached to clothing, the tiniest movements such as breath and pulse can be sensed.

The discovery opens up a host of possibilities for the development of wearable sensors from rubber, which could be used to monitor blood pressure, joint movement and respiration. Other applications of rubber-graphene sensors could be in the automotive industry (to develop sensitive airbags); in robotics, in medical device development (to monitor bodily motion), as early warning systems for cot death in babies or sleep apnoea in adults. They could also be woven into clothing to monitor athletes’ movement or for patients undergoing physical rehabilitation.

Professor Coleman said: “Sensors are becoming extremely important in medicine, wellness and exercise, medical device manufacturing, car manufacturing and robotics, among other areas. Biosensors, which are worn on or implanted into the skin, must be made of durable, flexible and stretchable materials that respond to the motion of the wearer. By implanting graphene into rubber, a flexible natural material, we are able to completely change its properties to make it electrically conductive, to develop a completely new type of sensor. Because rubber is available widely and cheaply, this unique discovery will open up major possibilities in sensor manufacturing worldwide.”

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

Sensitive, High-Strain, High-Rate Bodily Motion Sensors Based on Graphene–Rubber Composites by Conor S. Boland, Umar Khan, Claudia Backes, Arlene O’Neill, Joe McCauley, Shane Duane, Ravi Shanker, Yang Liu, Izabela Jurewicz, Alan B. Dalton, and Jonathan N. Coleman. ACS Nano, Article ASAP DOI: 10.1021/nn503454h Publication Date (Web): August 6, 2014

Copyright © 2014 American Chemical Society

This paper is open access (I was able to open the HTML version this morning, Aug. 20, 2014). As well the researchers have made this image illustrating their work available,

[downloaded from http://pubs.acs.org/doi/full/10.1021/nn503454h]

[downloaded from http://pubs.acs.org/doi/full/10.1021/nn503454h]