Tag Archives: biosensors

Food sensor made from of silk microneedles looks like velco

These sensors really do look like velcro,

The Velcro-like food sensor, made from an array of silk microneedles, can pierce through plastic packaging to sample food for signs of spoilage and bacterial contamination. Image: Felice Frankel

A September 9, 2020 news item on Nanowerk announces some research from the Massachusetts Institute (MIT),

MIT engineers have designed a Velcro-like food sensor, made from an array of silk microneedles, that pierces through plastic packaging to sample food for signs of spoilage and bacterial contamination.

The sensor’s microneedles are molded from a solution of edible proteins found in silk cocoons, and are designed to draw fluid into the back of the sensor, which is printed with two types of specialized ink. One of these “bioinks” changes color when in contact with fluid of a certain pH range, indicating that the food has spoiled; the other turns color when it senses contaminating bacteria such as pathogenic E. coli.

A Sept. 9, 2020 MIT news release (also on EurekAlert), which originated the news item, delves further into the research,

The researchers attached the sensor to a fillet of raw fish that they had injected with a solution contaminated with E. coli. After less than a day, they found that the part of the sensor that was printed with bacteria-sensing bioink turned from blue to red — a clear sign that the fish was contaminated. After a few more hours, the pH-sensitive bioink also changed color, signaling that the fish had also spoiled.

The results, published today in the journal Advanced Functional Materials, are a first step toward developing a new colorimetric sensor that can detect signs of food spoilage and contamination.

Such smart food sensors might help head off outbreaks such as the recent salmonella contamination in onions and peaches. They could also prevent consumers from throwing out food that may be past a printed expiration date, but is in fact still consumable.

“There is a lot of food that’s wasted due to lack of proper labeling, and we’re throwing food away without even knowing if it’s spoiled or not,” says Benedetto Marelli, the Paul M. Cook Career Development Assistant Professor in MIT’s Department of Civil and Environmental Engineering. “People also waste a lot of food after outbreaks, because they’re not sure if the food is actually contaminated or not. A technology like this would give confidence to the end user to not waste food.”

Marelli’s co-authors on the paper are Doyoon Kim, Yunteng Cao, Dhanushkodi Mariappan, Michael S. Bono Jr., and A. John Hart.

Silk and printing

The new food sensor is the product of a collaboration between Marelli, whose lab harnesses the properties of silk to develop new technologies, and Hart, whose group develops new manufacturing processes.

Hart recently developed a high-resolution floxography technique, realizing microscopic patterns that can enable low-cost printed electronics and sensors. Meanwhile, Marelli had developed a silk-based microneedle stamp that penetrates and delivers nutrients to plants. In conversation, the researchers wondered whether their technologies could be paired to produce a printed food sensor that monitors food safety.

“Assessing the health of food by just measuring its surface is often not good enough. At some point, Benedetto mentioned his group’s microneedle work with plants, and we realized that we could combine our expertise to make a more effective sensor,” Hart recalls.

The team looked to create a sensor that could pierce through the surface of many types of food. The design they came up with consisted of an array of microneedles made from silk.

“Silk is completely edible, nontoxic, and can be used as a food ingredient, and it’s mechanically robust enough to penetrate through a large spectrum of tissue types, like meat, peaches, and lettuce,” Marelli says.

A deeper detection

To make the new sensor, Kim first made a solution of silk fibroin, a protein extracted from moth cocoons, and poured the solution into a silicone microneedle mold. After drying, he peeled away the resulting array of microneedles, each measuring about 1.6 millimeters long and 600 microns wide — about one-third the diameter of a spaghetti strand.

The team then developed solutions for two kinds of bioink — color-changing printable polymers that can be mixed with other sensing ingredients. In this case, the researchers mixed into one bioink an antibody that is sensitive to a molecule in E. coli. When the antibody comes in contact with that molecule, it changes shape and physically pushes on the surrounding polymer, which in turn changes the way the bioink absorbs light. In this way, the bioink can change color when it senses contaminating bacteria.

The researchers made a bioink containing antibodies sensitive to E. coli, and a second bioink sensitive to pH levels that are associated with spoilage. They printed the bacteria-sensing bioink on the surface of the microneedle array, in the pattern of the letter “E,” next to which they printed the pH-sensitive bioink, as a “C.” Both letters initially appeared blue in color.

Kim then embedded pores within each microneedle to increase the array’s ability to draw up fluid via capillary action. To test the new sensor, he bought several fillets of raw fish from a local grocery store and injected each fillet with a fluid containing either E. coli, Salmonella, or the fluid without any contaminants. He stuck a sensor into each fillet. Then, he waited.

After about 16 hours, the team observed that the “E” turned from blue to red, only in the fillet contaminated with E. coli, indicating that the sensor accurately detected the bacterial antigens. After several more hours, both the “C” and “E” in all samples turned red, indicating that every fillet had spoiled.

The researchers also found their new sensor indicates contamination and spoilage faster than existing sensors that only detect pathogens on the surface of foods.

“There are many cavities and holes in food where pathogens are embedded, and surface sensors cannot detect these,” Kim says. “So we have to plug in a bit deeper to improve the reliability of the detection. Using this piercing technique, we also don’t have to open a package to inspect food quality.”

The team is looking for ways to speed up the microneedles’ absorption of fluid, as well as the bioinks’ sensing of contaminants. Once the design is optimized, they envision the sensor could be used at various stages along the supply chain, from operators in processing plants, who can use the sensors to monitor products before they are shipped out, to consumers who may choose to apply the sensors on certain foods to make sure they are safe to eat.

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

A Microneedle Technology for Sampling and Sensing Bacteria in the Food Supply Chain by Doyoon Kim, Yunteng Cao, Dhanushkodi Mariappan, Michael S. Bono Jr., A. John Hart, Benedetto Marelli. DOI: https://doi.org/10.1002/adfm.202005370 First published: 09 September 2020

This paper is behind a paywall.

You mean Fitbit makes mistakes? More accuracy with ‘drawn-on-skin’ electronics

A July 30, 2020 news item on ScienceDaily announces news about more accurate health monitoring with electronics applied directly to your skin,

A team of researchers led by Cunjiang Yu, Bill D. Cook Associate Professor of Mechanical Engineering at the University of Houston, has developed a new form of electronics known as “drawn-on-skin electronics,” allowing multifunctional sensors and circuits to be drawn on the skin with an ink pen.

The advance, the researchers report in Nature Communications, allows for the collection of more precise, motion artifact-free health data, solving the long-standing problem of collecting precise biological data through a wearable device when the subject is in motion.

The imprecision may not be important when your FitBit registers 4,000 steps instead of 4,200, but sensors designed to check heart function, temperature and other physical signals must be accurate if they are to be used for diagnostics and treatment.

A July 30, 2020 University of Houston news release (also on EurekAlert) by Jeannie Kever, which originated the news item, goes on to explain why you might want to have electronics ‘drawn on your skin’,

The drawn-on-skin electronics are able to seamlessly collect data, regardless of the wearer’s movements.  

They also offer other advantages, including simple fabrication techniques that don’t require dedicated equipment.

“It is applied like you would use a pen to write on a piece of paper,” said Yu. “We prepare several electronic materials and then use pens to dispense them. Coming out, it is liquid. But like ink on paper, it dries very quickly.”

Wearable bioelectronics – in the form of soft, flexible patches attached to the skin – have become an important way to monitor, prevent and treat illness and injury by tracking physiological information from the wearer. But even the most flexible wearables are limited by motion artifacts, or the difficulty that arises in collecting data when the sensor doesn’t move precisely with the skin.

The drawn-on-skin electronics can be customized to collect different types of information, and Yu said it is expected to be especially useful in situations where it’s not possible to access sophisticated equipment, including on a battleground.

The electronics are able to track muscle signals, heart rate, temperature and skin hydration, among other physical data, he said. The researchers also reported that the drawn-on-skin electronics have demonstrated the ability to accelerate healing of wounds.

In addition to Yu, researchers involved in the project include Faheem Ershad, Anish Thukral, Phillip Comeaux, Yuntao Lu, Hyunseok Shim, Kyoseung Sim, Nam-In Kim, Zhoulyu Rao, Ross Guevara, Luis Contreras, Fengjiao Pan, Yongcao Zhang, Ying-Shi Guan, Pinyi Yang, Xu Wang and Peng Wang, all from the University of Houston, and Jiping Yue and Xiaoyang Wu from the University of Chicago.

The drawn-on-skin electronics are actually comprised of three inks, serving as a conductor, semiconductor and dielectric.

“Electronic inks, including conductors, semiconductors, and dielectrics, are drawn on-demand in a freeform manner to develop devices, such as transistors, strain sensors, temperature sensors, heaters, skin hydration sensors, and electrophysiological sensors,” the researchers wrote.

This research is supported by the Office of Naval Research and National Institutes of Health.

Caption: A new form of electronics known as “drawn-on-skin electronics” allows multifunctional sensors and circuits to be drawn on the skin with an ink pen. Credit: University of Houston

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

Ultra-conformal drawn-on-skin electronics for multifunctional motion artifact-free sensing and point-of-care treatment by Faheem Ershad, Anish Thukral, Jiping Yue, Phillip Comeaux, Yuntao Lu, Hyunseok Shim, Kyoseung Sim, Nam-In Kim, Zhoulyu Rao, Ross Guevara, Luis Contreras, Fengjiao Pan, Yongcao Zhang, Ying-Shi Guan, Pinyi Yang, Xu Wang, Peng Wang, Xiaoyang Wu & Cunjiang Yu. Nature Communications volume 11, Article number: 3823 (2020) DOI: https://doi.org/10.1038/s41467-020-17619-1

This paper is open access.

Flexible graphene-rubber sensor for wearables

Courtesy: University of Waterloo

This waffled, greyish thing may not look like much but scientists are hopeful that it can be useful as a health sensor in athletic shoes and elsewhere. A March 6, 2020 news item on Nanowerk describes the work in more detail (Note: Links have been removed),

Researchers have utilized 3D printing and nanotechnology to create a durable, flexible sensor for wearable devices to monitor everything from vital signs to athletic performance (ACS Nano, “3D-Printed Ultra-Robust Surface-Doped Porous Silicone Sensors for Wearable Biomonitoring”).

The new technology, developed by engineers at the University of Waterloo [Ontario, Canada], combines silicone rubber with ultra-thin layers of graphene in a material ideal for making wristbands or insoles in running shoes.

A March 6, 2020 University of Waterloo news release, which originated the news item, delves further,

When that rubber material bends or moves, electrical signals are created by the highly conductive, nanoscale graphene embedded within its engineered honeycomb structure.

“Silicone gives us the flexibility and durability required for biomonitoring applications, and the added, embedded graphene makes it an effective sensor,” said Ehsan Toyserkani, research director at the Multi-Scale Additive Manufacturing (MSAM) Lab at Waterloo. “It’s all together in a single part.”

Fabricating a silicone rubber structure with such complex internal features is only possible using state-of-the-art 3D printing – also known as additive manufacturing – equipment and processes.

The rubber-graphene material is extremely flexible and durable in addition to highly conductive.

“It can be used in the harshest environments, in extreme temperatures and humidity,” said Elham Davoodi, an engineering PhD student at Waterloo who led the project. “It could even withstand being washed with your laundry.”

The material and the 3D printing process enable custom-made devices to precisely fit the body shapes of users, while also improving comfort compared to existing wearable devices and reducing manufacturing costs due to simplicity.

Toyserkani, a professor of mechanical and mechatronics engineering, said the rubber-graphene sensor can be paired with electronic components to make wearable devices that record heart and breathing rates, register the forces exerted when athletes run, allow doctors to remotely monitor patients and numerous other potential applications.

Researchers from the University of California, Los Angeles and the University of British Columbia collaborated on the project.

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

3D-Printed Ultra-Robust Surface-Doped Porous Silicone Sensors for Wearable Biomonitoring by Elham Davoodi, Hossein Montazerian, Reihaneh Haghniaz, Armin Rashidi, Samad Ahadian, Amir Sheikhi, Jun Chen, Ali Khademhosseini, Abbas S. Milani, Mina Hoorfar, Ehsan Toyserkani. ACS Nano 2020, 14, 2, 1520-1532 DOI: https://doi.org/10.1021/acsnano.9b06283 Publication Date: January 6, 2020 Copyright © 2020 American Chemical Society

This paper is behind a paywall.

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?