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A microscope for everyone: Researchers develop open-source optical toolbox

Modern microscopes used for biological imaging are expensive, are located in specialized laboratories and require highly qualified staff. To research novel, creative approaches to address urgent scientific issues — for example in the fight against infectious diseases such as Covid-19 — is thus primarily reserved for scientists at well-equipped research institutions in rich countries. A young research team from the Leibniz Institute of Photonic Technology (Leibniz IPHT) in Jena, the Friedrich Schiller University and Jena University Hospital wants to change this: The researchers have developed an optical toolbox to build microscopes for a few hundred euros that deliver high-resolution images comparable to commercial microscopes that cost a hundred to a thousand times more. With open-source blueprints, components from the 3D printer and smartphone camera, the UC2 (You. See. Too.) modular system can be combined specifically in the way the research question requires — from long-term observation of living organisms in the incubator to a toolbox for optics education.

The basic building block of the UC2 system is a simple 3D printable cube with an edge length of 5 centimeters, which can host a variety of components such as lenses, LEDs or cameras. Several such cubes are plugged on a magnetic raster base plate. Cleverly arranged, the modules thus result in a powerful optical instrument. An optical concept according to which focal planes of adjacent lenses coincide is the basis for most of the complex optical setups such as modern microscopes. With the UC2 toolbox, the research team of PhD students at the lab of Prof. Dr. Rainer Heintzmann, Leibniz IPHT and Friedrich Schiller University Jena, shows how this inherently modular process can be understood intuitively in hands-on-experiments. In this way, UC2 also provides users without technical training with an optical tool that they can use, modify and expand — depending on what they are researching.

Monitor pathogens — and then recycle the contaminated microscope

Helge Ewers, Professor of Biochemistry at the Free University of Berlin and the Charité, is investigating pathogens usind the UC2 toolbox. “The UC2 system allows us to produce a high-quality microscope at low cost, with which we can observe living cells in an incubator,” he states. UC2 thus opens up areas of application for biomedical research for which conventional microscopes are not suitable. “Commercial microscopes that can be used to examine pathogens over a longer period of time cost hundreds or thousands of times more than our UC2 setup,” says Benedict Diederich, PhD student at Leibniz-IPHT, who developed the optical toolbox there together with René Lachmann. “You can hardly get them into a contaminated laboratory from which you may not be able to remove them because they cannot be cleaned easily.” The UC2 microscope made of plastic, on the other hand, can be easily burned or recycled after its successful use in the biological safety laboratory. For a study at Jena University Hospital, the UC2 team observed the differentiation of monocytes into macrophages in the incubator over a period of one week in order to gain insights into how the innate immune system fights off pathogens in the body.

Building according to the Lego principle: From the idea to the prototype

Building according to the Lego principle — this not only awakens the users’ inner play instinct, observes the UC2 team, but it also opens up new possibilities for researchers to design an instrument precisely tailored to their research question. “With our method, it is possible to quickly assemble the right tool to map specific cells,” explains Benedict Diederich. “If, for example, a red wavelength is required as excitation, you simply install the appropriate laser and change the filter. If an inverted microscope is needed, you stack the cubes accordingly. With the UC2 system, elements can be combined depending on the required resolution, stability, duration or microscopy method and tested directly in the “rapid prototyping” process.

The Vision: Open Science

The researchers publish construction plans and software on the freely accessible online repository GitHub, so that the open-source community worldwide can access, rebuild, modify and expand the presented systems. “With the feedback from users, we improve the system step by step and add ever new creative solutions,” reports René Lachmann. The first users have already started to expand the system for themselves and their purposes. “We are eager to see when we can present the first user solutions.”

The aim behind this is to enable open science. Thanks to the detailed documentation, researchers can reproduce and further develop experiments anywhere in the world, even beyond well-equipped laboratories. “Change in Paradigm: Science for a Dime” is what Benedict Diederich calls this vision: to herald a paradigm shift in which the scientific process is as open and transparent as possible, freely accessible to all, where researchers share their knowledge with each other and incorporate it into their work.

UC2 experiment box brings science to schools

In order to get especially young people interested in optics, the research team has developed a sophisticated tool set for educational purposes in schools and universities. With “The Box” UC2 introduces a kit that enables users to learn about and try out optical concepts and microscopy methods. “The components can be combined to form a projector or a telescope; you can build a spectrometer or a smartphone microscope,” explains Barbora Maršíková, who developed experiments and a series of ready-to-use documentations that the UC2 team already tested in several workshops in and around Jena as well as in the US, in Great Britain and Norway. In Jena, the young researchers have already used the UC2 toolbox in several schools and e.g. supported pupils to build a fluorescence microscope to detect microplastics. “We have combined UC2 with our smartphone. This enabled us to build our own fluorescence microscope cost-effectively without any major optical knowledge and to develop a comparably simple method for detecting plastic particles in cosmetics,” reports Emilia Walther from the Montessori School in Jena, who together with her group is pursuing an innovative interdisciplinary learning approach.

“We want to make modern microscopy techniques accessible to a broad public,” says Benedict Diederich, “and build up an open and creative microscopy community.” This build-it-yourself approach to teaching has a huge potential, especially at times of the Corona pandemics, when access to teaching material at home is severely limited.

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Cutting edge technology to bioprint mini-kidneys

Researchers have used cutting edge technology to bioprint miniature human kidneys in the lab, paving the way for new treatments for kidney failure and possibly lab-grown transplants.

The study, led by the Murdoch Children’s Research Institute (MCRI) and biotech company Organovo and published in Nature Materials, saw the research team also validate the use of 3D bioprinted human mini kidneys for screening of drug toxicity from a class of drugs known to cause kidney damage in people.

The research showed how 3D bioprinting of stem cells can produce large enough sheets of kidney tissue needed for transplants.

Like squeezing toothpaste out of a tube, extrusion-based 3D bioprinting uses a ‘bioink’ made from a stem cell paste, squeezed out through a computer-guided pipette to create artificial living tissue in a dish.

MCRI researchers teamed up with San Diego based Organovo Inc to create the mini organs.

MCRI Professor Melissa Little, a world leader in modelling the human kidney, first began growing kidney organoids in 2015. But this new bio-printing method is faster, more reliable and allows the whole process to be scaled up. 3D bioprinting could now create about 200 mini kidneys in 10 minutes without compromising quality, the study found.

From larger than a grain of rice to the size of a fingernail, bioprinted mini-kidneys fully resemble a regular-sized kidney, including the tiny tubes and blood vessels that form the organ’s filtering structures called nephrons.

Professor Little said by using mini-organs her team hope to screen drugs to find new treatments for kidney disease or to test if a new drug was likely to injure the kidney.

“Drug-induced injury to the kidney is a major side effect and difficult to predict using animal studies. Bioprinting human kidneys are a practical approach to testing for toxicity before use,” she said.

In this study, the toxicity of aminoglycosides, a class of antibiotics that commonly damage the kidney, were tested.

“We found increased death of particular types of cells in the kidneys treated with aminoglycosides,” Professor Little said.

“By generating stem cells from a patient with a genetic kidney disease, and then growing mini kidneys from them, also paves the way for tailoring treatment plans specific to each patient, which could be extended to a range of kidney diseases.”

Professor Little said the study showed growing human tissue from stem cells also brought the promise of bioengineered kidney tissue.

“3D bioprinting can generate larger amounts of kidney tissue but with precise manipulation of biophysical properties, including cell number and conformation, improving the outcome,” she said.

Currently, 1.5 million Australians are unaware they are living with early signs of kidney disease such as decreased urine output, fluid retention and shortness of breath.

Professor Little said prior to this study the possibility of using mini kidneys to generate transplantable tissue was too far away to contemplate.

“The pathway to renal replacement therapy using stem cell-derived kidney tissue will need a massive increase in the number of nephron structures present in the tissue to be transplanted,” she said.

“By using extrusion bioprinting, we improved the final nephron count, which will ultimately determine whether we can transplant these tissues into people.”

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Laser technology: New trick for infrared laser pulses

Ordinary solid-state lasers, as used in laser pointers, generate light in the visible range. For many applications, however, such as the detection of molecules, radiation in the mid-infrared range is needed. Such infrared lasers are much more difficult to manufacture, especially if the laser radiation is required in the form of extremely short, intense pulses.

For a long time, scientists have been looking for simple methods to produce such infrared laser pulses — at the TU Wien this has now been achieved, in cooperation with Harvard University. The new technology does not require large experimental setups; it can be easily miniaturized and is therefore particularly interesting for practical applications. The new results have now been presented in the journal Nature Communications.

The frequency comb

“We generate laser light in the mid-infrared range with tailor-made quantum cascade lasers manufactured in the ultra-modern Nano-Center of TU Wien,” says Johannes Hillbrand from the Institute of Solid State Electronics at the TU Vienna, first author of the study. While in ordinary solid-state lasers the type of light emitted depends on the atoms in the material, in quantum cascade lasers tiny structures in the nanometer range are crucial. By designing these structures appropriately, the wavelength of the light can be precisely adjusted.

“Our quantum cascade lasers do not just deliver a single color of light, but a whole range of different frequencies,” says Ass.Prof. Benedikt Schwarz, who led the research work in his ERC grant funded project. “These frequencies are arranged very regularly, always with the same distance in between, like the teeth of a comb. Therefore, such a spectrum is called a frequency comb.”

Light is like a pendulum

However, it is not only the frequencies emitted by such a quantum cascade laser that are decisive, but also the phase with which the respective light waves oscillate. “You can compare this to two pendulums connected by a rubber band,” explains Johannes Hillbrand. “They can either swing back and forth, exactly in parallel, or opposite to each other, so that they either swing towards each other or away from each other. And these two vibration modes have slightly different frequencies.”

It is quite similar with laser light, which is composed of different wavelengths: The individual light waves of the frequency comb can oscillate exactly in sync — then they superimpose each other in an optimal way and can generate short, intense laser pulses. Or there can be shift between their oscillations, in which case no pulses are created, but laser light with an almost continuous intensity.

The light modulator

“In quantum cascade lasers, it has previously been difficult to switch back and forth between these two variants,” says Johannes Hillbrand. “However, we have built a tiny modulator into our quantum cascade laser, which the light waves pass by again and again.” An alternating electrical voltage is applied to this modulator. Depending on the frequency and strength of the voltage, different light oscillations can be excited in the laser.

“If you drive this modulator at exactly the right frequency, you can achieve that the different frequencies of our frequency comb all oscillate at exactly in sync,” says Benedikt Schwarz. “This makes it possible to combine these frequencies into short, intense laser pulses — more than 12 billion times per second.”

This level of control over short infrared laser pulses was previously not possible with semiconductor lasers. Similar types of light could at best only be generated using very expensive and lossy methods. “Our technology has the decisive advantage that it can be miniaturized,” emphasizes Benedikt Schwarz. “One could use it to build compact measuring instruments that use these special laser beams to search for very specific molecules in a gas sample, for example. Thanks to the high light intensity of the laser pulses, measurements that require two photons at the same time are also possible.

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After more than a decade, ChIP-seq may be quantitative after all

For more than a decade, scientists studying epigenetics have used a powerful method called ChIP-seq to map changes in proteins and other critical regulatory factors across the genome. While ChIP-seq provides invaluable insights into the underpinnings of health and disease, it also faces a frustrating challenge: its results are often viewed as qualitative rather than quantitative, making interpretation difficult.

But, it turns out, ChIP-seq may have been quantitative all along, according to a recent report selected as an Editors’ Pick by and featured on the cover of the Journal of Biological Chemistry.

“ChIP-seq is the backbone of epigenetics research. Our findings challenge the belief that additional steps are required to make it quantitative,” said Brad Dickson, Ph.D., a staff scientist at Van Andel Institute and the study’s corresponding author. “Our new approach provides a way to quantify results, thereby making ChIP-seq more precise, while leaving standard protocols untouched.”

Previous attempts to quantify ChIP-seq results have led to additional steps being added to the protocol, including the use of “spike-ins,” which are additives designed to normalize ChIP-seq results and reveal histone changes that otherwise may be obscured. These extra steps increase the complexity of experiments while also adding variables that could interfere with reproducibility. Importantly, the study also identifies a sensitivity issue in spike-in normalization that has not previously been discussed.

Using a predictive physical model, Dickson and his colleagues developed a novel approach called the sans-spike-in method for Quantitative ChIP-sequencing, or siQ-ChIP. It allows researchers to follow the standard ChIP-seq protocol, eliminating the need for spike-ins, and also outlines a set of common measurements that should be reported for all ChIP-seq experiments to ensure reproducibility as well as quantification.

By leveraging the binding reaction at the immunoprecipitation step, siQ-ChIP defines a physical scale for sequencing results that allows comparison between experiments. The quantitative scale is based on the binding isotherm of the immunoprecipitation products.

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Advanced atomic clock makes a better dark matter detector

JILA researchers have used a state-of-the-art atomic clock to narrow the search for elusive dark matter, an example of how continual improvements in clocks have value beyond timekeeping.

Older atomic clocks operating at microwave frequencies have hunted for dark matter before, but this is the first time a newer clock, operating at higher optical frequencies, and an ultra-stable oscillator to ensure steady light waves, have been harnessed to set more precise bounds on the search. The research is described in Physical Review Letters .

Astrophysical observations show that dark matter makes up most of the “stuff” in the universe but so far it has eluded capture. Researchers around the world have been looking for it in various forms. The JILA team focused on ultralight dark matter, which in theory has a teeny mass (much less than a single electron) and a humongous wavelength — how far a particle spreads in space — that could be as large as the size of dwarf galaxies. This type of dark matter would be bound by gravity to galaxies and thus to ordinary matter.

Ultralight dark matter is expected to create tiny fluctuations in two fundamental physical “constants”: the electron’s mass, and the fine-structure constant. The JILA team used a strontium lattice clock and a hydrogen maser (a microwave version of a laser) to compare their well-known optical and microwave frequencies, respectively, to the frequency of light resonating in an ultra-stable cavity made from a single crystal of pure silicon. The resulting frequency ratios are sensitive to variations over time in both constants. The relative fluctuations of the ratios and constants can be used as sensors to connect cosmological models of dark matter to accepted physics theories.

The JILA team established new limits on a floor for “normal” fluctuations, beyond which any unusual signals discovered later might be due to dark matter. The researchers constrained the coupling strength of ultralight dark matter to the electron mass and the fine-structure constant to be on the order of 10-5 (1 in 100,000) or less, the most precise measurement ever of this value.

JILA is jointly operated by the National Institute of Standards and Technology (NIST) and the University of Colorado Boulder.

“Nobody actually knows at what sensitivity level you will start to see dark matter in laboratory measurements,” NIST/JILA Fellow Jun Ye said. “The problem is that physics as we know it is not quite complete at this point. We know something is missing but we don’t quite know how to fix it yet.”

“We know dark matter exists from astrophysical observations, but we don’t know how the dark matter connects to ordinary matter and the values we measure,” Ye added. “Experiments like ours allow us to test various theory models people put together to try to explore the nature of dark matter. By setting better and better bounds, we hope to rule out some incorrect theory models and eventually make a discovery in the future.”

Scientists are not sure whether dark matter consists of particles or oscillating fields affecting local environments, Ye noted. The JILA experiments are intended to detect dark matter’s “pulling” effect on ordinary matter and electromagnetic fields, he said.

Atomic clocks are prime probes for dark matter because they can detect changes in fundamental constants and are rapidly improving in precision, stability and reliability. The cavity’s stability was also a crucial factor in the new measurements. The resonant frequency of light in the cavity depends on the length of the cavity, which can be traced back to the Bohr radius (a physical constant equal to the distance between the nucleus and the electron in a hydrogen atom). The Bohr radius is also related to the values of the fine structure constant and electron mass. Therefore, changes in the resonant frequency as compared to transition frequencies in atoms can indicate fluctuations in these constants caused by dark matter.

Researchers collected data on the strontium/cavity frequency ratio for 12 days with the clock running 30% of the time, resulting in a data set 978,041 seconds long. The hydrogen maser data spanned 33 days with the maser running 94% of the time, resulting in a 2,826,942-second record. The hydrogen/cavity frequency ratio provided useful sensitivity to the electron mass although the maser was less stable and produced noisier signals than the strontium clock.

JILA researchers collected the dark matter search data during their recent demonstration of an improved time scale — a system that incorporates data from multiple atomic clocks to produce a single, highly accurate timekeeping signal for distribution. As the performance of atomic clocks, optical cavities and time scales improves in the future, the frequency ratios can be re-examined with ever-higher resolution, further extending the reach of dark matter searches.

“Any time one is running an optical atomic time scale, there is a chance to set a new bound on or make a discovery of dark matter,” Ye said. “In the future, when we can put these new systems in orbit, it will be the biggest ‘telescope’ ever built for the search for dark matter.”

Funding was provided by NIST, the Defense Advanced Research Projects Agency and the National Science Foundation.

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Exoskeletons can reduce strain also in health care

Wearable exoskeletons are increasingly being used in physically demanding jobs to support good ergonomics and augment muscular strength. In ground-breaking studies led by researchers at Tampere University and LUT University in Finland, exoskeleton vests were worn by nurses to discover how the new technology would suit the special requirements of patient care.

According to Postdoctoral Research Fellow Tuuli Turja from Tampere University, Finnish nurses expect the new technologies to reduce physical strain.

“This message from the field led us to investigate what conditions exoskeletons would need to meet in order to reform nursing,” Turja says.

“Currently, exoskeletons are mainly used in manufacturing and logistics. Isn’t it high time to introduce exoskeletons in female-dominated sectors, where musculoskeletal disorders are rampant?” she continues.

In the field of care, exoskeleton-type technology is generally utilised in rehabilitation, where patients wear the skeleton of a walking robot, for example.

“However, in our study, a very different type of mobile and light exoskeleton was worn by nurses in patient care,” Turja explains.

The research article on the intention to use exoskeletons in geriatric care work was the first of its kind in the world. The peer-reviewed article was published in the journal Ergonomics in Design (link below), and it is openly available.

The article presents findings from two studies involving users of the Laevo Exoskeleton — a wearable back support vest, which, according to the manufacturer, alleviates lower back strain by 40-50%. In the first study, pairs of nursing students assisted geriatric patients in moving from a hospital bed into a wheelchair with and without the exoskeleton. In the second study, seven nurses tested the exoskeleton vest in a real care environment for a week.

The results show that due to the special characteristics of patient care, exoskeletons need to be developed further before being completely suitable for everyday nursing work. Nurses are willing to use exoskeletons to assist their work if the devices are comfortable and effortless to use and product development considers the requirements of nursing, such as interactive features and safety, in hectic work situations.

Looking like robots in the eyes of geriatric patients may be a downside, but the idea of making care work lighter with a slightly more agile and unobtrusive exoskeleton received the nurses’ approval.

The researchers ask whether the necessary product development could happen in Finland; perhaps Finnish manufacturers could make it possible for all the world’s caregivers to wear improved exoskeletons.

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Could megatesla magnetic fields be realized on Earth?

Magnetic fields are used in various areas of modern physics and engineering, with practical applications ranging from doorbells to maglev trains. Since Nikola Tesla’s discoveries in the 19th century, researchers have strived to realize strong magnetic fields in laboratories for fundamental studies and diverse applications, but the magnetic strength of familiar examples are relatively weak. Geomagnetism is 0.3-0.5 gauss (G) and magnetic tomography (MRI) used in hospitals is about 1 tesla (T = 104 G). By contrast, future magnetic fusion and maglev trains will require magnetic fields on the kilotesla (kT = 107 G) order. To date, the highest magnetic fields experimentally observed are on the kT order.

Recently, scientists at Osaka University discovered a novel mechanism called a “microtube implosion,” and demonstrated the generation of megatesla (MT = 1010G) order magnetic fields via particle simulations using a supercomputer. Astonishingly, this is three orders of magnitude higher than what has ever been achieved in a laboratory. Such high magnetic fields are expected only in celestial bodies like neutron stars and black holes.

Irradiating a tiny plastic microtube one-tenth the thickness of a human hair by ultraintense laser pulses produces hot electrons with temperatures of tens of billion of degrees. These hot electrons, along with cold ions, expand into the microtube cavity at velocities approaching the speed of light. Pre-seeding with a kT-order magnetic field causes the imploding charged particles infinitesimally twisted due to Lorenz force. Such a unique cylindrical flow collectively produces unprecedentedly high spin currents of about 1015 ampere/cm2 on the target axis and consequently, generates ultrahigh magnetic fields on the MT order.

The study conducted by Masakatsu Murakami and colleagues has confirmed that current laser technology can realize MT-order magnetic fields based on the concept. The present concept for generating MT-order magnetic fields will lead to pioneering fundamental research in numerous areas, including materials science, quantum electrodynamics (QED), and astrophysics, as well as other cutting-edge practical applications.

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Our health: New focus on the synergy effect of nanoparticles

Nanoparticles are used in a wide range of products and manufacturing processes because the properties of a material can change dramatically when the material comes down in nano-form.

They can be used, for example, to purify wastewater and to transport medicine around the body. They are also added to, for example, socks, pillows, mattresses, phone covers and refrigerators to supply the items with an antibacterial surface.

Much research has been done on how nanoparticles affect humans and the environment and a number of studies have shown that nanoparticles can disrupt or damage our cells.

This is confirmed by a new study that has also looked at how cells react when exposed to more than one kind of nano particle at the same time.

The lead author of the study is Barbara Korzeniowska from the Department of Biochemistry and Molecular Biology at SDU. The head of research is Professor Frank Kjeldsen from the same department.

His research into metal nanoparticles is supported by a European Research Grant of DKK 14 million.

“Throughout a lifetime, we are exposed to many different kinds of nano-particles, and we should investigate how the combination of different nano-particles affects us and also whether an accumulation through life can harm us,” says Barbara Korzeniowska.

She herself became interested in the subject when her little daughter one day was going in the bathtub and got a rubber duck as a toy.

“It turned out that it had been treated with nano-silver, probably to keep it free of bacteria, but small children put their toys in their mouths, and she could thus ingest nano-silver. That is highly worrying when research shows that nano-silver can damage human cells,” she says.

In her new study, she looked at nano-silver and nano-platinum. She has investigated their individual effect and whether exposure of both types of nanoparticles results in a synergy effect in two types of brain cells.

“There are almost no studies of the synergy effect of nano particles, so it is important to get started with these studies,” she says.

She chose nano-silver because it is already known to be able to damage cells and nano-platinum, because nano-platinum is considered to be so-called bio-inert; i.e. has a minimal interaction with human tissue.

The nanoparticles were tested on two types of brain cells: astrocytes and endothelial cells. Astrocytes are supporter cells in the central nervous system, which i.a. helps to supply the nervous system with nutrients and repair damage to the brain. Endothelial cells sit on the inside of the blood vessels and transport substances from the bloodstream to the brain.

When the endothelial cells were exposed to nano-platinum, nothing happened. When exposed to nano-silver, their ability to divide deteriorated. When exposed to both nano-silver and nano-platinum, the effect was amplified, and they died in large numbers. Furthermore, their defense mechanisms decreased, and they had difficulty communicating with each other.

“So even though nano-platinum alone does not do harm, something drastic happens when they are combined with a different kind of nano-particle,” says Frank Kjeldsen.

The astrocytes were more hardy and reacted “only” with impaired ability to divide when exposed to both types of nano-particles.

An earlier study, conducted by Frank Kjeldsen, has shown a dramatic synergy effect of silver nanoparticles and cadmium ions, which are found naturally all around us on Earth.

In that study, 72 % of the cells died (in this study it was intestinal cells) as they were exposed to both nano-silver and cadmium ions. When they were only exposed to nano-silver, 25% died. When exposed to cadmium ions only, 12% died.

We are involuntarily exposed

“Little is known about how large concentrations of nano-particles are used in industrial products. We also do not know what size particles they use — size also has an effect on whether they can enter a cell,” says Barbara Korzeniowska and continues:

“But we know that a lot of people are involuntarily exposed to nano-particles, and that there can be lifelong exposure.”

There are virtually no restrictions on adding nanoparticles to products. In the EU, however, manufacturers must have an approval if they want to use nanoparticles in products with antibacterial properties. In Denmark, they must also declare nano-content in such products on the label.

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Better material for wearable biosensors

Biosensors that are wearable on human skin or safely used inside the body are increasingly prevalent for both medical applications and everyday health monitoring. Finding the right materials to bind the sensors together and adhere them to surfaces is also an important part of making this technology better. A recent study from Binghamton University, State University of New York offers one possible solution, especially for skin applications.

Matthew S. Brown, a fourth-year PhD student with Assistant Professor Ahyeon Koh’s lab in the Department of Biomedical Engineering, served as the lead author for “Electronic?ECM: A Permeable Microporous Elastomer for an Advanced Bio-Integrated Continuous Sensing Platform,” published in the journal Advanced Materials Technology.

The study utilizes polydimethylsiloxane (PDMS), a silicone material popular for use in biosensors because of its biocompatibility and soft mechanics. It’s generally utilized as a solid film, nonporous material, which can lead to problems in sensor breathability and sweat evaporation.

“In athletic monitoring, if you have a device on your skin, sweat can build up under that device,” Brown said. “That can cause inflammation and also inaccuracies in continuous monitoring applications.

“For instance, one experiment with electrocardiogram (ECG) analysis showed that the porous PDMS allowed for the evaporation of sweat during exercise, capable of maintaining a high-resolution signal. The nonporous PDMS did not provide the ability for the sweat to readily evaporate, leading to a lower signal resolution after exercise.

The team created a porous PDMS material through electrospinning, a production method that makes nanofibers through the use of electric force.

During mechanical testing, the researchers found that this new material acted like the collagen and elastic fibers of the human epidermis. The material was also capable of acting as a dry adhesive for the electronics to strongly laminate on the skin, for adhesive-free monitoring. Biocompatibility and viability testing also showed better results after seven days of use, compared to the nonporous PDMS film.

“You can use this in a wide variety of applications where you need fluids to passively transfer through the material — such as sweat — to readily evaporate through the device,” Brown said.

Because the material’s permeable structure is capable of biofluid, small-molecule and gas diffusion, it can be integrated with soft biological tissue such as skin, neural and cardiac tissue with reduced inflammation at the application site.

Among the applications that Brown sees are electronics for healing long-term, chronic wounds; breathable electronics for oxygen and carbon dioxide respiratory monitoring; devices that integrate human cells within implantable electronic devices; and real-time, in-vitro chemical and biological monitoring.

Koh — whose recent projects include sweat-assisted battery power and biomonitoring — described the porous PDMS study as “a cornerstone of my research.”

“My lab is very interested in developing a biointegrated sensing system beyond wearable electronics,” she said. “At the moment, technologies have advanced to develop durable and flexible devices over the past 10 years. But we always want to go even further, to create sensors that can be used in more nonvisible systems that aren’t just on the skin.

“Koh also sees the possibilities for this porous PDMS material in another line of research she is pursuing with Associate Professor Seokheun Choi from the Department of Electrical and Computer Engineering. She and Choi are combining their strengths to create stretchable papers for soft bioelectronics, enabling us to monitor physiological statuses.

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Quantum light squeezes the noise out of microscopy signals

Researchers at the Department of Energy’s Oak Ridge National Laboratory used quantum optics to advance state-of-the-art microscopy and illuminate a path to detecting material properties with greater sensitivity than is possible with traditional tools.

“We showed how to use squeezed light — a workhorse of quantum information science — as a practical resource for microscopy,” said Ben Lawrie of ORNL’s Materials Science and Technology Division, who led the research with Raphael Pooser of ORNL’s Computational Sciences and Engineering Division. “We measured the displacement of an atomic force microscope microcantilever with sensitivity better than the standard quantum limit.”

Unlike today’s classical microscopes, Pooser and Lawrie’s quantum microscope requires quantum theory to describe its sensitivity. The nonlinear amplifiers in ORNL’s microscope generate a special quantum light source known as squeezed light.

“Imagine a blurry picture,” Pooser said. “It’s noisy and some fine details are hidden. Classical, noisy light prevents you from seeing those details. A ‘squeezed’ version is less blurry and reveals fine details that we couldn’t see before because of the noise.” He added, “We can use a squeezed light source instead of a laser to reduce the noise in our sensor readout.”

The microcantilever of an atomic force microscope is a miniature diving board that methodically scans a sample and bends when it senses physical changes. With student interns Nick Savino, Emma Batson, Jeff Garcia and Jacob Beckey, Lawrie and Pooser showed that the quantum microscope they invented could measure the displacement of a microcantilever with 50% better sensitivity than is classically possible. For one-second long measurements, the quantum-enhanced sensitivity was 1.7 femtometers — about twice the diameter of a carbon nucleus.

“Squeezed light sources have been used to provide quantum-enhanced sensitivity for the detection of gravitational waves generated by black hole mergers,” Pooser said. “Our work is helping to translate these quantum sensors from the cosmological scale to the nanoscale.”

Their approach to quantum microscopy relies on control of waves of light. When waves combine, they can interfere constructively, meaning the amplitudes of peaks add to make the resulting wave bigger. Or they can interfere destructively, meaning trough amplitudes subtract from peak amplitudes to make the resulting wave smaller. This effect can be seen in waves in a pond or in an electromagnetic wave of light like a laser.

“Interferometers split and then mix two light beams to measure small changes in phase that affect the interference of the two beams when they are recombined,” Lawrie said. “We employed nonlinear interferometers, which use nonlinear optical amplifiers to do the splitting and mixing to achieve classically inaccessible sensitivity.”

The interdisciplinary study, which is published in Physical Review Letters, is the first practical application of nonlinear interferometry.

A well-known aspect of quantum mechanics, the Heisenberg uncertainty principle, makes it impossible to define both the position and momentum of a particle with absolute certainty. A similar uncertainty relationship exists for the amplitude and phase of light.

That fact creates a problem for sensors that rely on classical light sources like lasers: The highest sensitivity they can achieve minimizes the Heisenberg uncertainty relationship with equal uncertainty in each variable. Squeezed light sources reduce the uncertainty in one variable while increasing the uncertainty in the other variable, thus “squeezing” the uncertainty distribution. For that reason, the scientific community has used squeezing to study phenomena both great and small.

The sensitivity in such quantum sensors is typically limited by optical losses. “Squeezed states are fragile quantum states,” Pooser said. “In this experiment, we were able to circumvent the problem by exploiting properties of entanglement.” Entanglement means independent objects behaving as one. Einstein called it “spooky action at a distance.” In this case, the intensities of the light beams are correlated with each other at the quantum level.

“Because of entanglement, if we measure the power of one beam of light, it would allow us to predict the power of the other one without measuring it,” he continued. “Because of entanglement, these measurements are less noisy, and that provides us with a higher signal to noise ratio.”

ORNL’s approach to quantum microscopy is broadly relevant to any optimized sensor that conventionally uses lasers for signal readout. “For instance, conventional interferometers could be replaced by nonlinear interferometry to achieve quantum-enhanced sensitivity for biochemical sensing, dark matter detection or the characterization of magnetic properties of materials,” Lawrie said.

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