Tag Archives: nanosensors

Detect lung cancer early by inhaling a nanosensor

The technology described in a January 5, 2024 news item on Nanowerk has not been tried in human clinical trials but early pre-clinical trial testing offers promise,

Using a new technology developed at MIT, diagnosing lung cancer could become as easy as inhaling nanoparticle sensors and then taking a urine test that reveals whether a tumor is present.

Key Takeaways

*This non-invasive approach may serve as an alternative or supplement to traditional CT scans, particularly beneficial in areas with limited access to advanced medical equipment.

*The technology focuses on detecting cancer-linked proteins in the lungs, with results obtainable through a simple paper test strip.

*Designed for early-stage lung cancer detection, the method has shown promise in animal models and may soon advance to human clinical trials.

*This innovation holds potential for significantly improving lung cancer screening and early detection, especially in low-resource settings.

A January 5, 2024 Massachusetts Institute of Technology (MIT) news release (also on EurkeAlert), which originated the news item, goes on to provide some technical details,

The new diagnostic is based on nanosensors that can be delivered by an inhaler or a nebulizer. If the sensors encounter cancer-linked proteins in the lungs, they produce a signal that accumulates in the urine, where it can be detected with a simple paper test strip.

This approach could potentially replace or supplement the current gold standard for diagnosing lung cancer, low-dose computed tomography (CT). It could have an especially significant impact in low- and middle-income countries that don’t have widespread availability of CT scanners, the researchers say.

“Around the world, cancer is going to become more and more prevalent in low- and middle-income countries. The epidemiology of lung cancer globally is that it’s driven by pollution and smoking, so we know that those are settings where accessibility to this kind of technology could have a big impact,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science.

Bhatia is the senior author of the paper, which appears today [January 5, 2024] in Science Advances. Qian Zhong, an MIT research scientist, and Edward Tan, a former MIT postdoc, are the lead authors of the study.

Inhalable particles

To help diagnose lung cancer as early as possible, the U.S. Preventive Services Task Force recommends that heavy smokers over the age of 50 undergo annual CT scans. However, not everyone in this target group receives these scans, and the high false-positive rate of the scans can lead to unnecessary, invasive tests.

Bhatia has spent the last decade developing nanosensors for use in diagnosing cancer and other diseases, and in this study, she and her colleagues explored the possibility of using them as a more accessible alternative to CT screening for lung cancer.

These sensors consist of polymer nanoparticles coated with a reporter, such as a DNA barcode, that is cleaved from the particle when the sensor encounters enzymes called proteases, which are often overactive in tumors. Those reporters eventually accumulate in the urine and are excreted from the body.

Previous versions of the sensors, which targeted other cancer sites such as the liver and ovaries, were designed to be given intravenously. For lung cancer diagnosis, the researchers wanted to create a version that could be inhaled, which could make it easier to deploy in lower resource settings.

“When we developed this technology, our goal was to provide a method that can detect cancer with high specificity and sensitivity, and also lower the threshold for accessibility, so that hopefully we can improve the resource disparity and inequity in early detection of lung cancer,” Zhong says.

To achieve that, the researchers created two formulations of their particles: a solution that can be aerosolized and delivered with a nebulizer, and a dry powder that can be delivered using an inhaler.

Once the particles reach the lungs, they are absorbed into the tissue, where they encounter any proteases that may be present. Human cells can express hundreds of different proteases, and some of them are overactive in tumors, where they help cancer cells to escape their original locations by cutting through proteins of the extracellular matrix. These cancerous proteases cleave DNA barcodes from the sensors, allowing the barcodes to circulate in the bloodstream until they are excreted in the urine.

In the earlier versions of this technology, the researchers used mass spectrometry to analyze the urine sample and detect DNA barcodes. However, mass spectrometry requires equipment that might not be available in low-resource areas, so for this version, the researchers created a lateral flow assay, which allows the barcodes to be detected using a paper test strip.

The researchers designed the strip to detect up to four different DNA barcodes, each of which indicates the presence of a different protease. No pre-treatment or processing of the urine sample is required, and the results can be read about 20 minutes after the sample is obtained.

“We were really pushing this assay to be point-of-care available in a low-resource setting, so the idea was to not do any sample processing, not do any amplification, just to be able to put the sample right on the paper and read it out in 20 minutes,” Bhatia says.

Accurate diagnosis

The researchers tested their diagnostic system in mice that are genetically engineered to develop lung tumors similar to those seen in humans. The sensors were administered 7.5 weeks after the tumors started to form, a time point that would likely correlate with stage 1 or 2 cancer in humans.

In their first set of experiments in the mice, the researchers measured the levels of 20 different sensors designed to detect different proteases. Using a machine learning algorithm to analyze those results, the researchers identified a combination of just four sensors that was predicted to give accurate diagnostic results. They then tested that combination in the mouse model and found that it could accurately detect early-stage lung tumors.

For use in humans, it’s possible that more sensors might be needed to make an accurate diagnosis, but that could be achieved by using multiple paper strips, each of which detects four different DNA barcodes, the researchers say.

The researchers now plan to analyze human biopsy samples to see if the sensor panels they are using would also work to detect human cancers. In the longer term, they hope to perform clinical trials in human patients. A company called Sunbird Bio has already run phase 1 trials on a similar sensor developed by Bhatia’s lab, for use in diagnosing liver cancer and a form of hepatitis known as nonalcoholic steatohepatitis (NASH).

In parts of the world where there is limited access to CT scanning, this technology could offer a dramatic improvement in lung cancer screening, especially since the results can be obtained during a single visit.

“The idea would be you come in and then you get an answer about whether you need a follow-up test or not, and we could get patients who have early lesions into the system so that they could get curative surgery or lifesaving medicines,” Bhatia says.

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

Inhalable point-of-care urinary diagnostic platform by Qian Zhong, Edward K. W. Tan, Carmen Martin-Alonso, Tiziana Parisi, Liangliang Hao, Jesse D. Kirkpatrick, Tarek Fadel, Heather E. Fleming, Tyler Jacks, and Sangeeta N. Bhatia. Science Advances 5 Jan 2024 Vol 10, Issue 1 DOI: 10.1126/sciadv.adj9591

This paper is open access.

Sunbird Bio (the company mentioned in the news release) can be found here.

Using carbon dots (organic nanosensors) to detect pesticides

Before getting to the latest about carbon dots, there’s something to be clarified (and it was news to me), a carbon dot is not a quantum dot. So says this 2020 paper, “Advances in carbon dots: from the perspective of traditional quantum dots” by Yanhong Liu, Hui Huang, Weijing Cao, Baodong Mao, Yang Liu, and Zhenhui Kang. Mater. Chem. Front., 2020,4, 1586-1613 First published March 17, 2020.

Abstract

Quantum dots (QDs) have been the core concept of nanoscience and nanotechnology since their inception, and play a dominant role in the development of the nano-field. Carbon dots (CDots), defined by a feature size of <10 nm, have become a rising star in the crossover field of carbon materials and traditional QDs (TQDs). CDots possess many unique structural, physicochemical and photochemical properties that render them a promising platform for biology, devices, catalysis and other applications. …

This story is about carbon dots but you can find out more about quantum dots in my October 6, 2023 posting concerning the 2023 Nobel prizes; scroll down to the ‘Chemistry’ subhead.

An August 30, 2023 news item on phys.org describes work from Concordia University (Montréal, Canada) on carbon dots,

Researchers at Concordia have developed a new system using tiny nanosensors called carbon dots to detect the presence of the widely used chemical glyphosate. Their research, titled “Ratiometric Sensing of Glyphosate in Water Using Dual Fluorescent Carbon Dots,” is published in Sensors.

An August 30, 2023 Concordia University news release (also on EurekAlert) by Patrick Lejtenyi, which originated the news item, explains the importance of the work and provides more technical details, Note: Links have been removed,

Glyphosate is a pesticide found in more than 750 agricultural, forestry, urban and home products, including Monsanto’s popular weed-killer Roundup. It is also controversial: studies have linked its overuse to environmental pollution and cancer in humans. Its sale is banned or restricted in dozens of countries and jurisdictions, including Canada.

The researchers’ system relies on the carbon dots’ chemical interaction with glyphosate to detect its presence. Carbon dots are exceedingly small fluorescent particles, usually no more than 10 or 15 nanometres in size (a human hair is between 80,000 and 100,000 nanometres). But when they are added to water solutions, these nanomaterials emit blue and red fluorescence.

The researchers employed an analysis technique called a ratiometric self-referencing assay to determine glyphosate levels in a solution. The red fluorescence emitted by the carbon dots when exposed to varying concentrations of the chemical and different pH levels is compared with a control in which no glyphosate is present. In all the tests, the blue fluorescence remained unchanged, giving the researchers a common reference point across the different tests.

They observed that higher levels of glyphosate quenched the red fluorescence, which they accredited to the interaction of the pesticide with the carbon dots’ surface.

“Our system differs from others because we are measuring the area between two peaks—two fluorescent signatures—on the visible spectrum,” says Adryanne Clermont-Paquette, a PhD candidate in biology and the paper’s lead author. “This is the integrated area between the two curves. Ratiometric measurement allows us to ignore variables such as temperature, pH levels or other environmental factors. That allows us to just only look at the levels of glyphosate and carbon dots that are in the system.”

“By understanding the chemistry at the surface of these very small dots and by knowing their optical properties, we can use them to our advantage for many different applications,” says Rafik Naccache, an associate professor of chemistry and biochemistry and the paper’s supervising author.

Research assistants Diego-Andrés Mendoza and Amir Sadeghi, along with associate professor of biology Alisa Piekny, are co-authors.

Starting small

Naccache says the technique is designed to detect minute amounts of the pesticide. The technique they developed is sensitive enough to be able to detect the presence of pesticide at levels as low as 0.03 parts per million.

“The challenge is always in the other direction, to see how low we can go in terms of sensitivity and selectivity,” he says.

There remains much work to be done before this technology can be used widely. But as Clermont-Paquette notes, this paper represents an important beginning.

“Understanding the interaction between glyphosate and carbon dots is a first step. If we are to move this along further, and develop it into a real-life application, we have to start with the fundamentals.”

The researchers are supported by funding from the Natural Sciences and Engineering Research Council of Canada.

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

Ratiometric Sensing of Glyphosate in Water Using Dual Fluorescent Carbon Dots
by Adryanne Clermont-Paquette, Diego-Andrés Mendoza, Amir Sadeghi, Alisa Piekny, and Rafik Naccache. Sensors 2023, 23(11), 5200; DOI: https://doi.org/10.3390/s23115200 Published: 30 May 2023

This paper is open access.

Nanosensors use AI to explore the biomolecular world

EPFL scientists have developed AI-powered nanosensors that let researchers track various kinds of biological molecules without disturbing them. Courtesy: École polytechnique fédérale de Lausanne (EPFL)

If you look at the big orange dot (representing the nanosensors?), you’ll see those purplish/fuschia objects resemble musical notes (biological molecules?). I think that brainlike object to the left and in light blue is the artificial intelligence (AI) component. (If anyone wants to correct my guesses or identify the bits I can’t, please feel free to add to the Comments for this blog.)

Getting back to my topic, keep the ‘musical notes’ in mind as you read about some of the latest research from l’École polytechnique fédérale de Lausanne (EPFL) in an April 7, 2021 news item on Nanowerk,

The tiny world of biomolecules is rich in fascinating interactions between a plethora of different agents such as intricate nanomachines (proteins), shape-shifting vessels (lipid complexes), chains of vital information (DNA) and energy fuel (carbohydrates). Yet the ways in which biomolecules meet and interact to define the symphony of life is exceedingly complex.

Scientists at the Bionanophotonic Systems Laboratory in EPFL’s School of Engineering have now developed a new biosensor that can be used to observe all major biomolecule classes of the nanoworld without disturbing them. Their innovative technique uses nanotechnology, metasurfaces, infrared light and artificial intelligence.

To each molecule its own melody

In this nano-sized symphony, perfect orchestration makes physiological wonders such as vision and taste possible, while slight dissonances can amplify into horrendous cacophonies leading to pathologies such as cancer and neurodegeneration.

An April 7, 2021 EPFL press release, which originated the news item, provides more detail,

“Tuning into this tiny world and being able to differentiate between proteins, lipids, nucleic acids and carbohydrates without disturbing their interactions is of fundamental importance for understanding life processes and disease mechanisms,” says Hatice Altug, the head of the Bionanophotonic Systems Laboratory. 

Light, and more specifically infrared light, is at the core of the biosensor developed by Altug’s team. Humans cannot see infrared light, which is beyond the visible light spectrum that ranges from blue to red. However, we can feel it in the form of heat in our bodies, as our molecules vibrate under the infrared light excitation.

Molecules consist of atoms bonded to each other and – depending on the mass of the atoms and the arrangement and stiffness of their bonds – vibrate at specific frequencies. This is similar to the strings on a musical instrument that vibrate at specific frequencies depending on their length. These resonant frequencies are molecule-specific, and they mostly occur in the infrared frequency range of the electromagnetic spectrum. 

“If you imagine audio frequencies instead of infrared frequencies, it’s as if each molecule has its own characteristic melody,” says Aurélian John-Herpin, a doctoral assistant at Altug’s lab and the first author of the publication. “However, tuning into these melodies is very challenging because without amplification, they are mere whispers in a sea of sounds. To make matters worse, their melodies can present very similar motifs making it hard to tell them apart.” 

Metasurfaces and artificial intelligence

The scientists solved these two issues using metasurfaces and AI. Metasurfaces are man-made materials with outstanding light manipulation capabilities at the nano scale, thereby enabling functions beyond what is otherwise seen in nature. Here, their precisely engineered meta-atoms made out of gold nanorods act like amplifiers of light-matter interactions by tapping into the plasmonic excitations resulting from the collective oscillations of free electrons in metals. “In our analogy, these enhanced interactions make the whispered molecule melodies more audible,” says John-Herpin.

AI is a powerful tool that can be fed with more data than humans can handle in the same amount of time and that can quickly develop the ability to recognize complex patterns from the data. John-Herpin explains, “AI can be imagined as a complete beginner musician who listens to the different amplified melodies and develops a perfect ear after just a few minutes and can tell the melodies apart, even when they are played together – like in an orchestra featuring many instruments simultaneously.” 

The first biosensor of its kind

When the scientists’ infrared metasurfaces are augmented with AI, the new sensor can be used to analyze biological assays featuring multiple analytes simultaneously from the major biomolecule classes and resolving their dynamic interactions. 

“We looked in particular at lipid vesicle-based nanoparticles and monitored their breakage through the insertion of a toxin peptide and the subsequent release of vesicle cargos of nucleotides and carbohydrates, as well as the formation of supported lipid bilayer patches on the metasurface,” says Altug.

This pioneering AI-powered, metasurface-based biosensor will open up exciting perspectives for studying and unraveling inherently complex biological processes, such as intercellular communication via exosomesand the interaction of nucleic acids and carbohydrates with proteins in gene regulation and neurodegeneration. 

“We imagine that our technology will have applications in the fields of biology, bioanalytics and pharmacology – from fundamental research and disease diagnostics to drug development,” says Altug. 

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

Infrared Metasurface Augmented by Deep Learning for Monitoring Dynamics between All Major Classes of Biomolecules by Aurelian John‐Herpin, Deepthy Kavungal. Lea von Mücke, Hatice Altug. Advanced Materials Volume 33, Issue 14 April 8, 2021 2006054 DOI: https://doi.org/10.1002/adma.202006054 First published: 22 February 2021

This paper is open access.

Living plants detect arsenic by way of embedded nanosensors

There’s a lot of arsenic in the world and it’s often a factor in making water undrinkable. When that water is used in farming It also pollutes soil and enters food-producing plants. A December 11, 2020 news item on Nanowerk announces research into arsenic detectors in plants,

Researchers have developed a living plant-based sensor that can in real-time detect and monitor levels of arsenic, a highly toxic heavy metal, in the soil. Arsenic pollution is a major threat to humans and ecosystems in many Asia Pacific countries.

Caption: Non-destructive plant nanobionic sensor embedded within leaves to report arsenic levels within plants to portable electronics, enabling real-time monitoring of arsenic uptake in living plants. Credit: Dr. Tedrick Thomas Salim Lew

I was not able to find the source for the news item but I did locate something close. From a December 13, 2020 Singapore-Massachusetts Institute of Technology (MIT) Alliance for Research and Technology (SMART), also on EurekAlert,

Scientists from the Disruptive and Sustainable Technologies for Agricultural Precision (DiSTAP) research group at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have engineered a novel type of plant nanobionic optical sensor that can detect and monitor, in real time, levels of the highly toxic heavy metal arsenic in the underground environment. This development provides significant advantages over conventional methods used to measure arsenic in the environment and will be important for both environmental monitoring and agricultural applications to safeguard food safety, as arsenic is a contaminant in many common agricultural products such as rice, vegetables, and tea leaves.

Arsenic and its compounds are a serious threat to humans and ecosystems. Long-term exposure to arsenic in humans can cause a wide range of detrimental health effects, including cardiovascular disease such as heart attack, diabetes, birth defects, severe skin lesions, and numerous cancers including those of the skin, bladder, and lung. Elevated levels of soil arsenic as a result of anthropogenic activities such as mining and smelting are also harmful to plants, inhibiting growth and resulting in substantial crop losses.

Food crops can absorb arsenic from the soil, leading to contamination of food and produce consumed by humans. Arsenic in underground environments can also contaminate groundwater and other underground water sources, the long-term consumption of which can cause severe health issues. As such, developing accurate, effective, and easy-to-deploy arsenic sensors is important to protect both the agriculture industry and wider environmental safety.

The novel optical nanosensors exhibit changes in their fluorescence intensity upon detecting arsenic. Embedded in plant tissues, with no detrimental effects on the plant, these sensors provide a nondestructive way to monitor the internal dynamics of arsenic taken up by plants from the soil. This integration of optical nanosensors within living plants enables the conversion of plants into self-powered detectors of arsenic from their natural environment, marking a significant upgrade from the time- and equipment-intensive arsenic sampling methods of current conventional methods.

“Our plant-based nanosensor is notable not only for being the first of its kind, but also for the significant advantages it confers over conventional methods of measuring arsenic levels in the below-ground environment, requiring less time, equipment, and manpower,” says Lew. “We envision that this innovation will eventually see wide use in the agriculture industry and beyond. I am grateful to SMART DiSTAP and the Temasek Life Sciences Laboratory (TLL), both of which were instrumental in idea generation and scientific discussion as well as research funding for this work.”

Besides detecting arsenic in rice and spinach, the team also used a species of fern, Pteris cretica, which can hyperaccumulate arsenic. This fern species can absorb and tolerate high levels of arsenic with no detrimental effect — engineering an ultrasensitive plant-based arsenic detector, capable of detecting very low concentrations of arsenic, as low as 0.2 parts per billion. In contrast, the regulatory limit for arsenic detectors is 10 parts per billion. Notably, the novel nanosensors can also be integrated into other species of plants. The researchers say this is the first successful demonstration of living plant-based sensors for arsenic and represents a groundbreaking advancement that could prove highly useful in both agricultural research (e.g., to monitor arsenic taken up by edible crops for food safety) and general environmental monitoring.

Previously, conventional methods of measuring arsenic levels included regular field sampling, plant tissue digestion, extraction, and analysis using mass spectrometry. These methods are time-consuming, require extensive sample treatment, and often involve the use of bulky and expensive instrumentation. The new approach couples nanoparticle sensors with plants’ natural ability to efficiently extract analytes via the roots and transport them. This allows for the detection of arsenic uptake in living plants in real time, with portable, inexpensive electronics such as a portable Raspberry Pi platform equipped with a charge-coupled device camera akin to a smartphone camera.

Co-author, DiSTAP co-lead principal investigator, and MIT Professor Michael Strano adds, “This is a hugely exciting development, as, for the first time, we have developed a nanobionic sensor that can detect arsenic — a serious environmental contaminant and potential public health threat. With its myriad advantages over older methods of arsenic detection, this novel sensor could be a game-changer, as it is not only more time-efficient, but also more accurate and easier to deploy than older methods. It will also help plant scientists in organizations such as TLL to further produce crops that resist uptake of toxic elements. Inspired by TLL’s recent efforts to create rice crops which take up less arsenic, this work is a parallel effort to further support SMART DiSTAP’s efforts in food security research, constantly innovating and developing new technological capabilities to improve Singapore’s food quality and safety.”

The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) program.

Led by MIT’s Strano and Singapore co-lead principal investigator Professor Chua Nam Hai, DiSTAP is one of the five Interdisciplinary Research Groups (IRGs) in SMART. The DiSTAP program addresses deep problems in food production in Singapore and the world by developing a suite of impactful and novel analytical genetic and biosynthetic technologies. The goal is to fundamentally change how plant biosynthetic pathways are discovered, monitored, engineered, and ultimately translated to meet the global demand for food and nutrients. Scientists from MIT, TTL, Nanyang Technological University, and National University of Singapore are collaboratively developing new tools for the continuous measurement of important plant metabolites and hormones for novel discovery, deeper understanding and control of plant biosynthetic pathways in ways not yet possible, especially in the context of green leafy vegetables; leveraging these new techniques to engineer plants with highly desirable properties for global food security, including high yield density production, drought and pathogen resistance and biosynthesis of high-value commercial products; developing tools for producing hydrophobic food components in industry-relevant microbes; developing novel microbial and enzymatic technologies to produce volatile organic compounds that can protect and/or promote growth of leafy vegetables; and applying these technologies to improve urban farming.

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

Plant Nanobionic Sensors for Arsenic Detection by Tedrick Thomas Salim Lew, Minkyung Park, Jianqiao Cui, Michael S. Strano. Advanced Materials DOI: https://doi.org/10.1002/adma.202005683 First published: 26 November 2020

This paper is behind a paywall.

Spinning gold out of nanocellulose

If you’re hoping for a Rumpelstiltskin reference (there is more about the fairy tale at the end of this posting) and despite the press release’s headline, you won’t find it in this August 10, 2020 news item on Nanowerk,

When nanocellulose is combined with various types of metal nanoparticles, materials are formed with many new and exciting properties. They may be antibacterial, change colour under pressure, or convert light to heat.

“To put it simply, we make gold from nanocellulose”, says Daniel Aili, associate professor in the Division of Biophysics and Bioengineering at the Department of Physics, Chemistry and Biology at Linköping University.

The research group, led by Daniel Aili, has used a biosynthetic nanocellulose produced by bacteria and originally developed for wound care. The scientists have subsequently decorated the cellulose with metal nanoparticles, principally silver and gold. The particles, no larger than a few billionths of a metre, are first tailored to give them the properties desired, and then combined with the nanocellulose.

An August 10, 2020 Linköping University press release (also on EurekAlert), which originated the news item,expands on a few details about the work (sob … without mentioning Rumpelstiltskin),

“Nanocellulose consists of thin threads of cellulose, with a diameter approximately one thousandth of the diameter of a human hair. The threads act as a three-dimensional scaffold for the metal particles. When the particles attach themselves to the cellulose, a material that consists of a network of particles and cellulose forms”, Daniel Aili explains.

The researchers can determine with high precision how many particles will attach, and their identities. They can also mix particles of different metals and with different shapes – spherical, elliptical and triangular.

In the first part of a scientific article published in Advanced Functional Materials, the group describes the process and explains why it works as it does. The second part focusses on several areas of application.

One exciting phenomenon is the way in which the properties of the material change when pressure is applied. Optical phenomena arise when the particles approach each other and interact, and the material changes colour. As the pressure increases, the material eventually appears to be gold.

“We saw that the material changed colour when we picked it up in tweezers, and at first we couldn’t understand why”, says Daniel Aili.

The scientists have named the phenomenon “the mechanoplasmonic effect”, and it has turned out to be very useful. A closely related application is in sensors, since it is possible to read the sensor with the naked eye. An example: If a protein sticks to the material, it no longer changes colour when placed under pressure. If the protein is a marker for a particular disease, the failure to change colour can be used in diagnosis. If the material changes colour, the marker protein is not present.

Another interesting phenomenon is displayed by a variant of the material that absorbs light from a much broader spectrum visible light and generates heat. This property can be used for both energy-based applications and in medicine.

“Our method makes it possible to manufacture composites of nanocellulose and metal nanoparticles that are soft and biocompatible materials for optical, catalytic, electrical and biomedical applications. Since the material is self-assembling, we can produce complex materials with completely new well-defined properties,” Daniel Aili concludes.

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

Self‐Assembly of Mechanoplasmonic Bacterial Cellulose–Metal Nanoparticle Composites by Olof Eskilson, Stefan B. Lindström, Borja Sepulveda, Mohammad M. Shahjamali, Pau Güell‐Grau, Petter Sivlér, Mårten Skog, Christopher Aronsson, Emma M. Björk, Niklas Nyberg, Hazem Khalaf, Torbjörn Bengtsson, Jeemol James, Marica B. Ericson, Erik Martinsson, Robert Selegård, Daniel Aili. Advanced Functional Materials DOI: https://doi.org/10.1002/adfm.202004766 First published: 09 August 2020

This paper is open access.

As for Rumpelstiltskin, there’s this abut the story’s origins and its cross-cultural occurrence, from its Wikipedia entry,

“Rumpelstiltskin” (/ˌrʌmpəlˈstɪltskɪn/ RUMP-əl-STILT-skin[1]) is a fairy tale popularly associated with Germany (where it is known as Rumpelstilzchen). The tale was one collected by the Brothers Grimm in the 1812 edition of Children’s and Household Tales. According to researchers at Durham University and the NOVA University Lisbon, the story originated around 4,000 years ago.[2][3] However, many biases led some to take the results of this study with caution.[4]

The same story pattern appears in numerous other cultures: Tom Tit Tot in England (from English Fairy Tales, 1890, by Joseph Jacobs); The Lazy Beauty and her Aunts in Ireland (from The Fireside Stories of Ireland, 1870 by Patrick Kennedy); Whuppity Stoorie in Scotland (from Robert Chambers’s Popular Rhymes of Scotland, 1826); Gilitrutt in Iceland; جعيدان (Joaidane “He who talks too much”) in Arabic; Хламушка (Khlamushka “Junker”) in Russia; Rumplcimprcampr, Rampelník or Martin Zvonek in the Czech Republic; Martinko Klingáč in Slovakia; “Cvilidreta” in Croatia; Ruidoquedito (“Little noise”) in South America; Pancimanci in Hungary (from A Csodafurulya, 1955, by Emil Kolozsvári Grandpierre, based on the 19th century folktale collection by László Arany); Daiku to Oniroku (大工と鬼六 “A carpenter and the ogre”) in Japan and Myrmidon in France.

An earlier literary variant in French was penned by Mme. L’Héritier, titled Ricdin-Ricdon.[5] A version of it exists in the compilation Le Cabinet des Fées, Vol. XII. pp. 125-131.

The Cornish tale of Duffy and the Devil plays out an essentially similar plot featuring a “devil” named Terry-top.

All these tales are Aarne–Thompson type 500, “The Name of the Helper”.[6]

Should you be curious about the story as told by the Brothers Grimm, here’s the beginning to get you started (from the grimmstories.com Rumpelstiltskin webpage),

There was once a miller who was poor, but he had one beautiful daughter. It happened one day that he came to speak with the king, and, to give himself consequence, he told him that he had a daughter who could spin gold out of straw. The king said to the miller: “That is an art that pleases me well; if thy daughter is as clever as you say, bring her to my castle to-morrow, that I may put her to the proof.”

When the girl was brought to him, he led her into a room that was quite full of straw, and gave her a wheel and spindle, and said: “Now set to work, and if by the early morning thou hast not spun this straw to gold thou shalt die.” And he shut the door himself, and left her there alone. And so the poor miller’s daughter was left there sitting, and could not think what to do for her life: she had no notion how to set to work to spin gold from straw, and her distress grew so great that she began to weep. Then all at once the door opened, and in came a little man, who said: “Good evening, miller’s daughter; why are you crying?”

Enjoy! BTW, should you care to, you can find three other postings here tagged with ‘Rumpelstiltskin’. I think turning dross into gold is a popular theme in applied science.

Herbicide nanometric sensor could help diagnose multiple sclerosis

This research into nanometric sensors and multiple sclerosis comes from Brazil. According to a June 23, 2015 news item on Nanowerk (Note: A link has been removed),

The early diagnosis of certain types of cancer, as well as nervous system diseases such as multiple sclerosis and neuromyelitis optica, may soon be facilitated by the use of a nanosensor capable of identifying biomarkers of these pathological conditions (“A Nanobiosensor Based on 4-Hydroxyphenylpyruvate Dioxygenase Enzyme for Mesotrione Detection”).

The nanobiosensor was developed at the Federal University of São Carlos (UFSCar), Sorocaba, in partnership with the São Paulo Federal Institute of Education, Science & Technology (IFSP), Itapetininga, São Paulo State, Brazil. It was originally designed to detect herbicides, heavy metals and other pollutants.

A June 23, 2015 Fundação de Amparo à Pesquisa do Estado de São Paulo news release on EurekAlert, which originated the news item, describes the sensor as it was originally used and explains its new function as a diagnostic tool for multiple sclerosis and other diseases,

“It’s a highly sensitive device, which we developed in collaboration with Alberto Luís Dario Moreau, a professor at IFSP. “We were able to increase sensitivity dramatically by going down to the nanometric scale,” said physicist Fábio de Lima Leite, a professor at UFSCar and the coordinator of the research group.

The nanobiosensor consists of a silicon nitride (Si3N4) or silicon (Si) nanoprobe with a molecular-scale elastic constant and a nanotip coupled to an enzyme, protein or other molecule.

When this molecule touches a target of interest, such as an antibody or antigen, the probe bends as the two molecules adhere. The deflection is detected and measured by the device, enabling scientists to identify the target.

“We started by detecting herbicides and heavy metals. Now we’re testing the device for use in detecting target molecules typical of nervous system diseases, in partnership with colleagues at leading centers of research on demyelinating diseases of the central nervous system”

The migration from herbicide detection to antibody detection was motivated mainly by the difficulty of diagnosing demyelinating diseases, cancer and other chronic diseases before they have advanced beyond an initial stage.

The criteria for establishing a diagnosis of multiple sclerosis or neuromyelitis optica are clinical (supplemented by MRI scans), and patients do not always present with a characteristic clinical picture. More precise diagnosis entails ruling out several other diseases.

The development of nanodevices will be of assistance in identifying these diseases and reducing the chances of false diagnosis.

The procedure can be as simple as placing a drop of the patient’s cerebrospinal fluid on a glass slide and observing its interaction with the nanobiosensor.

“If the interaction is low, we’ll be able to rule out multiple sclerosis with great confidence,” Leite said. “High interaction will indicate that the person is very likely to have the disease.” In this case, further testing would be required to exclude the possibility of a false positive.

“Different nervous system diseases have highly similar symptoms. Multiple sclerosis and neuromyelitis optica are just two examples. Even specialists experience difficulties or take a long time to diagnose them. Our technique would provide a differential diagnostic tool,” Leite said.

The next step for the group is to research biomarkers for these diseases that have not been completely mapped, including antibodies and antigens, among others. The group has begun tests for the detection of head and neck cancer.

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

A Nanobiosensor Based on 4-Hydroxyphenylpyruvate Dioxygenase Enzyme for Mesotrione Detection by P. Soto Garcia, A.L.D Moreau, J.C. Magalhaes Ierich,  A.C Araujo Vig, A.M. Higa, G.S. Oliveira, F. Camargo Abdalla, M. Hausen, & F.L. Leite. Sensors Journal, IEEE  (Volume:15 ,  Issue: 4) pp. 2106 – 2113 Date of Publication: 20 November 2014 Date of Current Version: 27 January 2015 Issue Date: April 2015  DOI 10.1109/JSEN.2014.2371773

This paper is behind a paywall.

From monitoring glucose in kidneys to climate change in trees

That headline is almost poetic but I admit It’s a bit of a stretch rhymewise, kidneys/trees. In any event, a Feb. 6, 2015 news item on Azonano describes research into monitoring the effects of climate change on trees,

Serving as a testament to the far-reaching impact of Governor Andrew M. Cuomo’s commitment to maintaining New York State’s global leadership in nanotechnology innovation, SUNY Polytechnic Institute’s Colleges of Nanoscale Science and Engineering (SUNY Poly CNSE) today announced the National Science Foundation (NSF) has awarded $837,000 to support development of a first of its kind nanoscale sensor to monitor the effects of climate change on trees.

A Feb. 5, 2015 SUNY Poly CNSE news release, which originated the news item, provides more details including information about the sensor’s link to measuring glucose in kidneys,

The NSF grant was generated through the Instrument Development for Biological Research (IDBR) program, which provides funds to develop new classes of devices for bio-related research. The NANAPHID, a novel aphid-like nanosensor, will provide real-time measurements of carbohydrates in live plant tissue. Carbohydrate levels in trees are directly connected to plant productivity, such as maple sap production and survival. The NANAPHID will enable researchers to determine the effects of a variety of environmental changes including temperature, precipitation, carbon dioxide, soil acidity, pests and pathogens. The nanosensor can also provide real-time monitoring of sugar concentration levels, which are of signficant importance in maple syrup production and apple and grape farming.

“The technology for the NANAPHID is rooted in a nanoscale sensor SUNY Poly CNSE developed to monitor glucose levels in human kidneys being prepared for transplant. Our team determined that certain adjustments would enable the sensor to provide similar monitoring for plants, and provide a critical insight to the effects of climate change on the environment,” said Dr. James Castracane, professor and head of the Nanobioscience Constellation at SUNY Polytechnic Institute. “This is a perfect example of the cycle of innovation made possible through the ongoing nanotechnology research and development at SUNY Poly CNSE’s NanoTech Complex.”

“This new sensor will be used in several field experiments on measuring sensitivity of boreal forest to climate warming. Questions about forest response to rising air and soil temperatures are extremely important for forecasting future atmospheric carbon dioxide levels, climate change and forest health,” said Dr. Andrei Lapenas, principal investigator and associate professor of climatology at the University at Albany. “At the same time, we already see some potential commercial application for NANAPHID-type sensors in agriculture, food industry and other fields. Our collaboration with SUNY Poly CNSE has been extremely productive and I look forward to continuing our work together.”

The NANAPHID project began in 2014 with a $135,000 SUNY Research Foundation Network of Excellence grant. SUNY Poly CNSE will receive $400,000 of the NSF award for the manufacturing aspects of the sensor array development and testing. The remaining funds will be shared between Dr. Lapenas and researchers Dr. Ruth Yanai (ESF), Dr. Thomas Horton (ESF), and Dr. Pamela Templer (Boston University) for data collection and analysis.

“With current technology, analyzing carbohydrates in plant tissues requires hours in the lab or more than $100 a sample if you want to send them out. And you can’t sample the same tissue twice, the sample is destroyed in the analysis,” said Dr. Yanai. “The implantable device will be cheap to produce and will provide continuous monitoring of sugar concentrations, which is orders of magnitude better in both cost and in the information provided. Research questions we never dreamed of asking before will become possible, like tracking changes in photosynthate over the course of a day or along the stem of a plant, because it’s a nondestructive assay.”

“I see incredible promise for the NANAPHID device in plant ecology. We can use the sensors at the root tip where plants give sugars to symbiotic fungi in exchange for soil nutrients,” said Dr. Horton. “Some fungi are believed to be significant carbon sinks because they produce extensive fungal networks in soils and we can use the sensors to compare the allocation of photosynthate to roots colonized by these fungi versus the allocation to less carbon demanding fungi. Further, the vast majority of these symbiotic fungi cannot be cultured in lab. These sensors will provide valuable insights into plant-microbe interactions under field conditions.”

“The creation of this new sensor will make understanding the effects of a variety of environmental changes, including climate change, on the health and productivity of forests much easier to measure,” said Dr. Templer. “For the first time, we will be able to measure concentrations of carbohydrates in living trees continuously and in real-time, expanding our ability to examine controls on photosynthesis, sap flow, carbon sequestration and other processes in forest ecosystems.”

Fascinating, eh? I wonder who made the connection between human kidneys and plants and how that person made the connection.

The Danish ‘Mini-mouth and wine

Denmark is not the first country that pops to mind when there’s mention of a nanosensor that mimics what happens in your mouth when you drink wine but that’s where the device was developed. From a Sept. 17, 2014 news item on ScienceDaily,

When wine growers turn their grapes into wine, they need to control a number of processes to bring out the desired flavour in the product that ends up in the wine bottle. An important part of the taste is known in wine terminology as astringency, and it is characteristic of the dry sensation you get in your mouth when you drink red wine in particular. It is the tannins in the wine that bring out the sensation that — otherwise beyond compare — can be likened to biting into an unripe banana. It is mixed with lots of tastes in the wine and feels both soft and dry.

Researchers at the Interdisciplinary Nanoscience Centre (iNANO ), Aarhus University, have now developed a nanosensor that is capable of measuring the effect of astringency in your mouth when you drink wine.

A Sept. 17, 2014 Aarhus University (Denmark) press release (also on EurekAlert), which originated the news item, provides a general description of the sensor,

… To put it simply, the sensor is a kind of mini-mouth that uses salivary proteins to measure the sensation that occurs in your mouth when you drink wine. The researchers are looking at how the proteins change in the interaction with the wine, and they can use this to describe the effect of the wine.

There is great potential in this – both for the wine producers and for research into the medicine of the future. Indeed, it is the first time that a sensor has been produced that not only measures the amount of proteins and molecules in your mouth when you drink wine, but also measures the effect of wine – or other substances – entering your mouth.

The wine producers’ perspective is introduced (from the news release),

The sensor makes it possible for wine producers to control the development of astringency during wine production because they can measure the level of astringency in the wine right from the beginning of the process. This can currently only be achieved when the wine is ready and only by using a professional tasting panel – with the associated risk of human inaccuracy. Using the sensor, producers can work towards the desired sensation of dryness before the wine is ready.

“We don’t want to replace the wine taster. We just want a tool that is useful in wine production. When you produce wine, you know that the finished product should have a distinct taste with a certain level of astringency. If it doesn’t work, people won’t drink the wine,” says PhD student Joana Guerreiro, first author of the scientific article in ACS NANO, which presents the sensor and its prospects.

Better Understanding of Astringency

There are many different elements in wine that create astringency, and this makes it difficult to measure because there are so many parameters. The sensor turns this upside down by measuring the molecules in your mouth instead.

“The sensor expands our understanding of the concept of astringency. The sensation arises because of the interaction between small organic molecules in the wine and proteins in your mouth. This interaction gets the proteins to change their structure and clump together. Until now, the focus has been on the clumping together that takes place fairly late in the process. With the sensor, we’ve developed a method that mimics the binding and change in the structure of the proteins, i.e. the early part of the process. It’s a more sensitive method, and it reproduces the effect of the astringency better,” says Joana Guerreiro.

There are also some technical details in the news release,

Quite specifically, the sensor is a small plate coated with nanoscale gold particles. On this plate, the researchers simulate what happens in your mouth by first adding some of the proteins contained in your saliva. After this they add the wine. The gold particles on the plate act as nano-optics and make it possible to focus a beam of light below the diffraction limit so as to precisely measure something that is very small – right down to 20 nanometres. This makes it possible to study and follow the proteins, and to see what effect the wine has. It is thereby possible to see the extent to which the small molecules have to bind together for the clumping effect on the protein to be set off.

The technique in itself is not new. What is new is using it to create a sensor that can measure an effect rather than just a number of molecules. In this case, the effect is the dry sensation you get in your mouth when you drink wine. However, it is also possible to use the sensor to measure other effects.

Here’s a look at the Mini-mouth,

PhD student Joana Guerreiro has taken part in developing a sensor, which - by using nanoscience - can measure how we experience the feeling of dryness in wine. Photo: Lars Kruse, Aarhus University.

PhD student Joana Guerreiro has taken part in developing a sensor, which – by using nanoscience – can measure how we experience the feeling of dryness in wine. Photo: Lars Kruse, Aarhus University.

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

Multifunctional Biosensor Based on Localized Surface Plasmon Resonance for Monitoring Small Molecule–Protein Interaction by Joana Rafaela Lara Guerreiro, Maj Frederiksen, Vladimir E. Bochenkov, Victor De Freitas, Maria Goreti Ferreira Sales, and Duncan Steward Sutherland. ACS Nano, 2014, 8 (8), pp 7958–7967 DOI: 10.1021/nn501962y Publication Date (Web): July 8, 2014

Copyright © 2014 American Chemical Society

This paper is behind a paywall.

ETA Sept. 19, 2014: Dexter Johnson provides some insight into the field of ‘artificial mouths’ in his Sept. 18, 2014 posting (Nanoclast blog on the IEEE [Institute of Electrical and Electronics Engineers] about the work in Denmark.

Israeli scientists help us “sniff out” bombs

A July 23, 2014 news item on ScienceDaily describes the situation regarding bombs and other explosive devices and the Israelie research,

Security forces worldwide rely on sophisticated equipment, trained personnel, and detection dogs to safeguard airports and other public areas against terrorist attacks. A revolutionary new electronic chip with nano-sized chemical sensors is about to make their job much easier.

The groundbreaking nanotechnology-inspired sensor, devised by Prof. Fernando Patolsky of Tel Aviv University’s School of Chemistry and Center for Nanoscience and Nanotechnology, and developed by the Herzliya company Tracense, picks up the scent of explosives molecules better than a detection dog’s nose. Research on the sensor was recently published in the journal Nature Communications.

Existing explosives sensors are expensive, bulky and require expert interpretation of the findings. In contrast, the new sensor is mobile, inexpensive, and identifies in real time — and with great accuracy — explosives in the air at concentrations as low as a few molecules per 1,000 trillion.

A July 23, 2014 American Friends of Tel Aviv University news release (also on EurekAlert), which originated the news item, gives more detail about the research and potential product,

“Using a single tiny chip that consists of hundreds of supersensitive sensors, we can detect ultra low traces of extremely volatile explosives in air samples, and clearly fingerprint and differentiate them from other non-hazardous materials,” said Prof. Patolsky, a top researcher in the field of nanotechnology. “In real time, it detects small molecular species in air down to concentrations of parts-per-quadrillion, which is four to five orders of magnitude more sensitive than any existing technological method, and two to three orders of magnitude more sensitive than a dog’s nose.

“This chip can also detect improvised explosives, such as TATP (triacetone triperoxide), used in suicide bombing attacks in Israel and abroad,” Prof. Patolsky added.

The clusters of nano-sized transistors used in the prototype are extremely sensitive to chemicals, which cause changes in the electrical conductance of the sensors upon surface contact. When just a single molecule of an explosive comes into contact with the sensors, it binds with them, triggering a rapid and accurate mathematical analysis of the material.

“Animals are influenced by mood, weather, state of health and working hours, the oversaturation of olfactory system, and much more,” said Prof. Patolsky. “They also cannot tell us what they smell. Automatic sensing systems are superior candidates to dogs, working at least as well or better than nature. This is not an easy task, but was achieved through the development of novel technologies such as our sensor.”

The trace detector, still in prototype, identifies several different types of explosives several meters from the source in real time. It has been tested on the explosives TNT, RDX, and HMX, used in commercial blasting and military applications, as well as peroxide-based explosives like TATP and HMTD. The latter are commonly used in homemade bombs and are very difficult to detect using existing technology.

“Our breakthrough has the potential to change the way hazardous materials are detected, and of course should provide populations with more security,” said Prof. Patolsky. “The faster, more sensitive detection of tiny amounts of explosives in the air will provide for a better and safer world.”

Tracense has invested over $10M in research and development of the device since 2007, and expects to go to market next year [2015]. Prof.Patolsky and his team of researchers are currently performing multiple and extensive field tests of prototype devices of the sensor.

Here’s a link to and a citation for a recent paper by Professor Patolsky and his team,

Supersensitive fingerprinting of explosives by chemically modified nanosensors arrays by Amir Lichtenstein, Ehud Havivi, Ronen Shacham, Ehud Hahamy, Ronit Leibovich, Alexander Pevzner, Vadim Krivitsky, Guy Davivi, Igor Presman, Roey Elnathan, Yoni Engel, Eli Flaxer, & Fernando Patolsky. Nature Communications 5, Article number: 4195 doi:10.1038/ncomms5195 Published 24 June 2014 Updated online 09 July 2014

This paper is behind a paywall but a free preview is available via ReadCube Access.

Your plant feeling stressed? Have we got a nanosensor for you!

An April 15, 2014 news item on ScienceDaily features an intriguing application for nansensors on plants that may have an important impact as we deal with the problems associated with droughts. This work comes from the University of California at San Diego (UCSD),

Biologists have succeeded in visualizing the movement within plants of a key hormone responsible for growth and resistance to drought. The achievement will allow researchers to conduct further studies to determine how the hormone helps plants respond to drought and other environmental stresses driven by the continuing increase in the atmosphere’s carbon dioxide, or CO2, concentration.

The April 15, 2014 UCSD news release by Kim McDonald, which originated the news item, describes the plant hormone being tracked and the tracking tool developed by the researchers,

The plant hormone the biologists directly tracked is abscisic acid, or ABA, which plays a major role in activating drought resistance responses of plants and in regulating plant growth under environmental stress conditions. The ABA stress hormone also controls the closing of stomata, the pores within leaves through which plants lose 95 percent of their water while taking in CO2 for growth.

Scientists already know the general role that ABA plays within plants, but by directly visualizing the hormone they can now better understand the complex interactions involving ABA when a plant is subjected to drought or other stress.

“Understanding the dynamic distribution of ABA in plants in response to environmental stimuli is of particular importance in elucidating the action of this important plant hormone,” says Julian Schroeder, a professor of biology at UC San Diego who headed the research effort. “For example, we can now investigate whether an increase in the leaf CO2 concentration that occurs every night due to respiration in leaves affects the ABA concentration in stomatal cells.”

The researchers developed what they call a “genetically-encoded reporter” in order to directly and instantaneously observe the movements of ABA within the mustard plant Arabidopsis. These reporters, called “ABAleons,” contain two differentially colored fluorescent proteins attached to an ABA-binding sensor protein. Once bound to ABA, the ABAleons change their fluorescence emission, which can be analyzed using a microscope. The researchers showed that ABA concentration changes and waves of ABA movement could be monitored in diverse tissues and individual cells over time and in response to stress.

“Using this reporter, we directly observed long distance ABA movements from the stem of a germinating seedling to the leaves and roots of the growing plant and, for the first time, we were able to determine the rate of ABA movement within the growing plant,” says Schroeder.

“Using this tool, we now can detect ABA in live plants and see how it is distributed,” says Rainer Waadt, a postdoctoral associate in Schroeder’s laboratory and the first author of the paper. “We are also able to directly see that environmental stress causes an increase in the ABA concentration in the stomatal guard cells that surround each stomatal pore. In the future, our sensors can be used to study ABA distribution in response to different stresses, including CO2 elevations, and to identify other molecules and proteins that affect the distribution of this hormone. We can also learn how fast plants respond to stresses and which tissues are important for the response.”

The researchers demonstrated that their new ABA nanosensors also function effectively as isolated proteins. This means that the sensors could be directly employed using state-of-the-art high-throughput screening platforms to screen for chemicals that could activate or enhance a drought resistance response. The scientists say such chemicals could become useful in the future for enhancing a drought resistance response, when crops experience a severe drought, like the one that occurred in the Midwest in the summer of 2012.

The scientists have provided a 1 min. 30 sec. (roughly) video where you can watch a vastly speeded up version of the process (Courtesy: UCSD),

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

FRET-based reporters for the direct visualization of abscisic acid concentration changes and distribution in Arabidopsis by Rainer Waadt, Kenichi Hitomi, Noriyuki Nishimura, Chiharu Hitomi, Stephen R Adams, Elizabeth D Getzoff, & Julian I Schroeder. eLife 2014;3:e01739 DOI: http://dx.doi.org/10.7554/eLife.01739 Published April 15, 2014

This paper is open access.