This research has been ongoing in School of Physics Professor Flavio Fenton’s lab with his student Noah DeTal and research scientist Abouzar Kaboudian. Their latest findings are published in the paper, “Terminating Spiral Waves with a Single Designed Stimulus: Teleportation as the Mechanism for Defibrillation,” in the journal Proceedings of the National Academy of Science.

The Problem with Spiral Waves

Electrical waves enable the heart to contract and send blood throughout the body. When a wave becomes a spiral, its rotation is faster than the heart’s natural pacemaker and suppresses normal cardiac function. Instead, one spiral wave can spawn more spirals until the heart is overtaken by multiple spiral waves, leading to disorganized contraction, and preventing the heart from supplying the body with blood.

For years, scientists and doctors have worked to find the best way to stop spiral waves before they get out of control. Yet for over half a century the best method has been a single strong electric shock. The 300 joules of energy required for defibrillation excites not just the heart cells, but the entire body, making it very painful for the patient.

Over the years researchers have experimented with using weaker shocks to reorganize arrythmias.

“We still did not have a clear understanding of how defibrillation worked,” said Fenton. “This research explains the minimum energy required to actually terminate an arrhythmia and I believe it clarifies the mechanism for defibrillation.”

The Symmetrical Solution

The researchers determined that because spiral waves develop in pairs, they must also be terminated in pairs. Every spiral wave is connected to another spiral going in the opposite direction. Bringing the spiral waves together through an electric shock instantly eliminates both waves.

The researchers used a mathematical method to identify the key regions for electrical shock stimulation to target spiral waves. They determined that a stimulus delivered to the tissue areas a spiral wave just left and were able sustain a new wave could defibrillate the heart.

In the process of terminating the spiral waves, the researchers were actually moving them, as well, through a concept they named “teleportation.”

“We call it teleportation because it’s very similar to what you see in science fiction where something is moved instantaneously from one place to another,” Fenton said.

Spiral waves can be teleported anywhere in the heart using this approach. In particular, spiral waves can be moved so that they collide with their partners, which extinguishes them. Fenton explained that for successful defibrillation to occur, all pairs of spiral waves must be eliminated in this manner.

The researchers plan to further test this concept using two-dimensional cultures of heart cells.

“The next step is to is to prove experimentally that what we did numerically is possible,” Fenton said.

Eventually, Fenton added, they want to develop methods that could be used clinically, and are partnering with cardiologists at Emory University on this work.

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Most biological materials, for example, amino acids, fossils, sedimentary rocks, plants, microbes, proteins and lipids, have strong organic fluorescence signals that can be detected by specialized scanning cameras. In a study published in Nature Scientific Reports recently, the research team reported that the Biofinder is so sensitive that it can accurately detect the bio-residue in fish fossils from the 34-56 million year-old Green River formation.

“The Biofinder is the first system of its kind,” said Anupam Misra, lead instrument developer and researcher at the Hawai’i Institute of Geophysics and Planetology at the UH Manoa School of Ocean and Earth Science and Technology (SOEST). “At present, there is no other equipment that can detect minute amounts of bio-residue on a rock during the daytime. Additional strengths of the Biofinder are that it works from a distance of several meters, takes video and can quickly scan a large area.”

Though the Biofinder was first developed in 2012 by Misra, advances supported by the NASA PICASSO program culminated in the latest color version of the compact Biofinder.

Finding evidence of biological residue in a vast planetary landscape is an enormous challenge. So, the team tested the Biofinder’s detection abilities on the ancient Green River fish fossils and corroborated the results through laboratory spectroscopy analysis, scanning electron microscopy and fluorescence lifetime imaging microscopy.

“There are some unknowns regarding how quickly bio-residues are replaced by minerals in the fossilization process,” said Misra. “However, our findings confirm once more that biological residues can survive millions of years, and that using biofluorescence imaging effectively detects these trace residues in real time.”

The search for life — which may be existing or extinct — on planetary bodies is one of the major goals of planetary exploration missions conducted by NASA and other international space agencies.

“If the Biofinder were mounted on a rover on Mars or another planet, we would be able to rapidly scan large areas quickly to detect evidence of past life, even if the organism was small, not easy to see with our eyes, and dead for many millions of years,” said Misra. “We anticipate that fluorescence imaging will be critical in future NASA missions to detect organics and the existence of life on other planetary bodies.”

“The Biofinder’s capabilities would be critical for NASA’s Planetary Protection program, for the accurate and no-invasive detection of contaminants such as microbes or extraterrestrial biohazards to or from planet Earth,” said Sonia J. Rowley, the team biologist and co-author on the study.

Misra and colleagues are applying to have the opportunity to send the Biofinder on a future NASA mission.

“The detection of such biomarkers would constitute groundbreaking evidence for life outside of planet Earth,” said Misra.

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Materials provided by University of Hawaii at Manoa. Original written by Marcie Grabowski. Note: Content may be edited for style and length.

A new study published today reveals that population declines have been greatest among species that migrate to areas with more human infrastructure — roads, buildings, power lines, wind turbines — as well as higher population densities and hunting levels.

Habitat degradation and climate change have also played a part in driving long-term declines.

The research team hope their work will help inform how best to target conservation efforts.

Dr James Gilroy, from UEA’s School of Environmental Sciences, said: “We know that migratory birds are in greater decline than non-migratory species, but it’s not clear why.

“We wanted to find out where in their life cycles these migratory species are most exposed to human impacts.”

The research team identified 16 human-induced threats to migratory birds, including infrastructure associated with bird disturbance and collisions, conversion of land from natural habitat to human land use, and climate change.

Advances in satellite imagery allowed the team to map each of the 16 threats across Europe, Africa and Western Asia. The team also created the first ever large-scale map of hunting pressure across the region.

A total of 103 species of migrating birds were studied, including many rapidly declining species like the Turtle Dove and the Common Cuckoo, using large-scale datasets.

The team calculated ‘threat scores’ for factors such as habitat loss and climate change, across breeding locations, as well as non-breeding ranges.

They then explored the relationships between these threat scores and bird population trends calculated from 1985 to 2018 by the Pan-European Common Bird Monitoring Scheme (PECBMS).

Dr C,laire Buchan from UEA’s School of Biological Sciences, said: “We found that human modification of the landscape in the birds’ distribution ranges in Europe, Africa and Western Asia is associated with declining numbers of over 100 Afro-Eurasian migratory birds.

“When we talk about modification of the landscape, we mean things like roads, buildings, powerlines, wind turbines — anything that isn’t naturally there.

“One of the biggest impacts seems to be caused by things that would kill a bird outright — for example flying into a wind turbine, a building, being electrocuted on a powerline, hit by a vehicle or hunted. We found that exposure to these human-induced ‘direct mortality’ threats in the bird’s wintering ranges are reflected in population decreases in breeding birds.”

Dr Aldina Franco, also from UEA’s School of Environmental Sciences, said: “Our findings are important because we need to understand where declining species are being most impacted by humans across their seasonal migrations. Pinpointing where birds are most exposed to these threats could help us target conservation actions.”

This research was led by UEA (UK) in collaboration with the University of Porto and the University of Lisbon (both Portugal), and the Czech Society for Ornithology (Czech Republic).

Researchers working on this project have received funding from the Natural Environment Research Council (NERC), the European Commission and the Portuguese Foundation for Science and Technology.

The findings, published in the journal Science Advances, identify AVG-388 as the lead drug candidate, which effectively blocks the activity of the viral RNA polymerase, an enzyme responsible for replication of the viral genome. RSV is a leading cause of lower respiratory infections in infants and immunocompromised individuals, but no efficient therapeutic exists. The virus caused an estimated 33.1 million cases worldwide in 2015 that required 3.2 million hospitalizations and resulted in 59,800 deaths.

Finding effective drugs to fight RSV has been challenging. Through mutations, RSV has escaped advanced candidate classes that prevent the virus from entering a cell. To overcome this issue, recent drug development efforts have focused on the viral RNA-dependent RNA polymerase complex of RSV because of the possible broader window of opportunity to fight the virus during viral genome replication and transcription.

“We have identified the AVG class of inhibitors of RSV RNA synthesis,” said Dr. Richard K. Plemper, senior author of the study, Distinguished University Professor and director of the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State. “Through chemical optimization, we have developed the clinical candidate AVG-388, which is orally efficacious against RSV in animal models of infection.”

In addition, the researchers demonstrated potent antiviral activity in human airway epithelium organoid cultures.

“In this study, we have mapped an exciting druggable target in the RSV RNA-dependent RNA-polymerase and established the clinical potential of the AVG inhibitor class against RSV disease,” said Dr. Julien Sourimant, first author of the study and a postdoctoral fellow in the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State.

The research team investigated the effect of treatment on viral replication at different oral doses intended to prevent or cure disease. They demonstrated that treatment reduced virus load by several orders of magnitude in the different disease models.

“Our results lay the foundation for formal development of the AVG class and the structure-guided identification of companion drugs with overlapping target sites but distinct resistance profiles,” Plemper said.

Co-authors of the study include Julien Sourimant (first author), Carolin M. Lieber, Jeong-Joong Yoon, Mart Toots and Richard K. Plemperof the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State; Mugunthan Govindarajan, Venkata Udumula and Michael G. Natchusof Emory Institute for Drug Development at Emory University; Kaori Sakamotoof the College of Veterinary Medicine at the University of Georgia; Joseph Pattiof Aviragen Therapeutics Inc. (now at JP Biotech Advisors Inc.); and John Vernachioof Aviragen Therapeutics Inc.

The study was funded by the National Institutes of Health.

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Writing in the June 24, 2022 issue of Science Advances, scientists at University of California San Diego School of Medicine and elsewhere report on the molecular impact of life indoors, describing how the presence of humans interacts with their microbial roommates, changing the home’s biology and chemistry.

The findings, suggest the authors, should influence future building designs.

Modern Americans spend approximately 70 percent of their time inside, reshaping the indoor microbiome with inputs from their bodies. Limited research has investigated the interaction between humans and indoor exposures to specific pollutants, toxins and particles, but the new study more ambitiously documents how people influence the entire molecular and chemical composition of a home through routine activities.

An experimental test home was erected in Austin, Texas during the summer of 2018. The house was designed for ordinary use and included bathrooms, a kitchen, gathering and work areas. Overnight stays were prohibited, but 45 study participants, plus visitors, spent time in the house, occupying it for approximately six hours per day for 26 days, during which they performed scripted activities, such as cooking, cleaning and socializing.

Researchers sampled the distribution of detectable molecules and microbes throughout the occupied areas of the house at the beginning of the experiment, dubbed T1, and again 28 days later, dubbed T2, largely by swabbing surfaces and conducting different genomic, metabolic and chemical analyses.

Before T1, the house was deep cleaned with a bleach solution. Nonetheless, researchers said traces of molecules associated with humans were still present. At T2, after almost of month of human occupation, the house was alive with molecular and microbial abundance and diversity, albeit unevenly distributed.

Researchers found molecules associated with skin care products, skin cells, drugs (such as antidepressants and anabolic steroids), food-derived molecules (such as terpenes and flavonoids), human or animal metabolites (molecules generated during the process of metabolism, such as bile and fatty acids), amino acids, sugars and microbial metabolites.

Most of the indoor surface molecules were natural products (biologically produced molecules rather than synthetic compounds), food, molecules associated with the outdoors, personal care products and human-derived metabolites, often traced to fecal matter.

Food, human-associated microbes, feces, building materials and the microbes that grow upon them and building materials in humid conditions were deemed the likely primary sources.

Not surprisingly, the kitchen and toilet were hotspots of molecular and microbial diversity, though numbers fluctuated with surface cleaning and sanitation. “It appears that, even when a subset of chemistry is removed because of the cleaning, it is only temporary and/or partial, as the sum total of cleaning and human activities overall results in an increase in accumulation of richer chemistry,” the authors wrote.

Surfaces routinely touched by people, such as tables, light switches and knobs, were more abundant in molecular and microbial chemistry. Floors showed less molecular diversity, perhaps because they were cleaned more often. Windows, chairs and doors not routinely touched by human occupants displayed the least change in chemical diversity between T1 and T2.

Other residents

Of course, people weren’t the only occupants of the test home. Researchers found indoor surfaces covered with bacteria, fungi and other microbes, plus their metabolites. Regular cleaning altered these microbial populations and diversity over time, allowing different species to recolonize cleaned spaces.

At the end of the test period, less than half of the house’s original microbiome remained, but it accounted from more than 96 percent of all microbial life counted. Most of the detected microbiome at T2 was derived from human occupants, mainly commensal species that reside on human skin or in the gut. Free-living, environment-associated microbes had been depleted by human activities. In other words, cleaned or pushed out.

“We don’t know exactly how the human-related microbes squeezed out the environmental microbes because there are many ways this could happen, but it’s clear that they do,” said Rob Knight, PhD, one of the study’s principal investigators and director of the Center for Microbiome Innovation at UC San Diego. “Understanding this phenomenon will be a key goal of future research on the microbiology of the built environment.”

The authors noted that at least 1 percent of the detected indoor molecules may pose an outsized health effect. For example, the bacterial species Paenibacillus was associated with molecules from coffee, one of the dominant sources of food-derived indoor molecules detected. In the home, especially at T2, Paenibacillus was observed in and around the area where coffee was prepared and the genus has been found to grow in coffee machines. Paenibacillus species have been used as probiotics in chickens and bees, and may also contribute to human health, consistent with recent reports that coffee drinking is associated with improved cardiovascular health and longevity.

“Understanding specifically how our observations that both human and microbial occupants change the chemical make-up of a home should influence building material design to improve human health will require additional studies,” said co-principle investigator Pieter Dorrestein, PhD, director of the Collaborative Mass Spectrometry Innovation Center at Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego.

Co-authors include: Alexander A. Aksenov and Alexey V. Melnik, UC San Diego and University of Connecticut; Rodolfo A. Salido, Caitriona Brennan, Asker Brejnrod, Andrés Mauricio Caraballo-Rodríguez, Julia M. Gauglitz and Franck Lejzerowicz, Delphine K. Farmer, Colorado State University; and Marina E. Vance, University of Colorado Boulder.

After that, all growth of the heart comes from enlargement of existing cells, not from creation of new muscle cells. In an adult heart attack, heart failure results when the lost cardiomyocytes are replaced by fibrous scar tissue, instead of new muscle cells. This starts a vicious cycle of heart enlargement, loss of pumping function and eventual death.

In 2020, University of Alabama at Birmingham researchers reported that surgery to remove the left ventricle apex of the heart of pigs, one day after birth, somehow extended the replication ability of heart muscle cells. In fact, after such surgery, pigs can completely recover from a heart attack four weeks after birth, without scarring or decline in heart function.

To better understand the underlying gene expression changes in this extended regeneration window, UAB researchers now report nuclear RNA-sequencing of heart muscle cells, using this porcine model. From such knowledge, and much further research yet to come, clinicians may potentially learn how to regenerate adult heart cardiomyocytes after a heart attack.

This study, led by Jianyi “Jay” Zhang, M.D., Ph.D., chair of the UAB Department of Biomedical Engineering, is published as a Circulation research letter.

The researchers compared nuclei from heart tissue of five groups of pigs. Two groups were regeneration models that had left ventricle apical resections, or AR, at postnatal day one, or P1. One of those two groups then had ligation of the left anterior descending coronary artery four weeks after birth, or P28, to induce a myocardial infarction, or MI; this group is called AR_P1MI_P28. The other group, called AR_P1, did not have ligation.

Two non-regenerative controls did not have the P1 apical resection, but one of those did have the induced heart attack at P28. Those two groups were called Control and MI_P28.

Hearts were removed for single-nucleus RNA-sequencing at P30 through P56 for the AR_P1MI_P28 animals, and hearts from all other groups were explanted for sequencing on P1, P28 or P56.

The fifth group were fetal hearts, or FH, at embryonic day 80.

A total of 218,945 high-quality nuclei were captured, and a network biology clustering analysis identified all eight major heart cell types. Complete gene nucleus data were available for 94,844 cardiomyocytes. The cardiomyocytes were distributed among six clusters, named cardiomyocyte 1 through cardiomyocyte 6.

Three clusters were almost entirely composed of cardiomyocytes from a single experimental group: cardiomyocyte 2 from control-P56, cardiomyocyte 3 from control-P1, and cardiomyocyte 6 from FH.

The cardiomyocyte 4 and 5 clusters contained primarily AR_P1MI_P28-P35 cardiomyocytes. The cardiomyocyte 1 cluster included cardiomyocytes from all other animal groups and time points and a small number of AR_P1MI_P28-P35 cardiomyocytes, but few fetal or control-P56 cardiomyocytes.

The cardiomyocyte 4 and 5 clusters that contained primarily AR_P1MI_P28-P35 cardiomyocytes showed increased cell cycle activity and proliferation, changes that helped remuscularize the left ventricle after experimental heart attack, without scarring. The researchers also found 506 genes that were positively correlated with the highly proliferative AR_P1MI_P28-P30 and AR_P1MI_P28-P35 cardiomyocytes; these genes participated in pathways that regulated heart development, cell proliferation and cardiomyocyte proliferation.

“It will be interesting to examine these two distinct cell populations from the AR_P1MI_P28 injury in future studies,” Zhang said. “The findings are highly impactful because they show, for the first time, that the left ventricle can remuscularize the myocardial infarct beyond postnatal day seven, or P7, in large mammals. These observations provide a foundation for future investigations of the molecular mechanisms and signaling molecules that regulate the injury-induced preservation of cardiomyocyte cell cycle activity in newborn large mammals, and ultimately to remuscularize the heart muscle in patients suffering from heart attacks, thus preventing heart failure.”

The study is titled “Single nucleus transcriptomics: Apical resection in newborn pigs extends the time window of cardiomyocyte proliferation and myocardial regeneration.” Co-authors with Zhang are Yuji Nakada, Yang Zhou, Eric Y. Zhang, Yuhua Wei, Meng Zhao, Wangping Chen, Jiacheng Sun and S. Naqi Raza, UAB Department of Biomedical Engineering; Thanh Nguyen and Jake Y. Chen, UAB Informatics Institute; Gregory P. Walcott, UAB Department of Medicine, Division of Cardiovascular Disease; and Wuming Gong, Erik Skie and Daniel J. Garry, School of Medicine, University of Minnesota, Minneapolis.

Support came from National Institutes of Health grants HL114120, HL131017, HL149137 and HL134764.

At UAB, Zhang holds the T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership. Biomedical Engineering is a joint department of the UAB Marnix E. Heersink School of Medicine and the UAB School of Engineering. The Informatics Institute and the Department of Medicine are part of the Heersink School of Medicine.

“Organic semiconductors offer several distinct advantages over conventional silicon-based semiconducting devices: they are made from abundantly available elements, such as carbon, hydrogen and nitrogen; they offer mechanical flexibility and low cost of manufacture; and they can be fabricated easily at scale,” notes UC Santa Barbara engineering professor Yon Visell, part of a group of researchers working with the new materials. “Perhaps more importantly, the polymers themselves can be crafted using a wide variety of chemistry methods to endow the resulting semiconducting devices with interesting optical and electrical properties. These properties can be designed, tuned or selected in many more ways than can inorganic (e.g., silicon-based) transistors.”

The design flexibility that Visell describes is exemplified in the reconfigurability of the devices reported by UCSB researchers and others in the journal Advanced Materials.

Reconfigurable logic circuits are of particular interest as candidates for post-CMOS electronics, because they make it possible to simplify circuit design while increasing energy efficiency. One recently developed class of carbon-based (as opposed to, say, silicon- or gallium-nitride-based) transistors), called organic electrochemical transistors(OECTs), have been shown to be well-suited for reconfigurable electronics.

In the recent paper, chemistry professorThuc-Quyen Nguyen,who leads the UCSB Center for Polymers and Organic Solids, and co-authors including Visell describe a breakthrough material — a soft, semiconducting carbon-based polymer — that can provide unique advantages over the inorganic semiconductors currently found in conventional silicon transistors.

“Reconfigurable organic logic devices are promising candidates for the next generations of efficient computing systems and adaptive electronics,” the researchers write. “Ideally, such devices would be of simple structure and design, [as well as] power-efficient and compatible with high-throughput microfabrication techniques.”

Conjugating for Conductivity

A conjugated polyelectrolyte, or CPE-K, consists of a central conjugated backbone, with alternating single and double bonds, and multiple charged side chains with ions attached. “Having conjugated bonds throughout the polymer makes it conductive, because the delocalized electrons have high mobility across the length of the polymer,” explains lead author Tung Nguyen-Dang, a postdoctoral researcher in Nguyen’s lab who is co-advised by Visell. “You are marrying two classic materials, the polymer and the semiconductor, in this molecular design.”

Artificial intelligence (AI) played a role in developing the material. “You can proceed by trial and error to make a material,” Nguyen says. “You can make a whole bunch of them and hope for the best, and maybe one out of twenty works or has interesting properties; however, we worked with a professor at California State Northridge, Gang Lu, who used AI to select building blocks and do calculations to get a rough idea of how to proceed, given the energy level and properties we were aiming for.”

Figuring out Reconfigurability

One key benefit of CPE-K is that it enables reconfigurable (“dual-mode”) logic gates, meaning they can be switched on the fly to operate in either depletion mode or accumulation mode, simply by adjusting the voltage at the gate. In depletion mode, current flowing through the active material between the drain and the source is initially high, before application of any gate voltage (a.k.a. the ON state). When the gate voltage is applied, the current drops and the transistor is turned to an OFF state. Accumulation mode is the opposite — without gate voltage, the transistor is in an OFF position, and applying a gate voltage yields higher current, switching the device to an ON state.

“Conventional electronic logic gates, which are the building blocks for all digital circuits found in computers or smart phones, are hardware that do only the one job they are designed for,” says Nguyen. “For instance, an AND gate has two inputs and one output, and if the inputs applied to it are all 1, then the output will be 1. Similarly, a NOR gate also has two inputs and one output, but if all of the inputs applied to it are 1, then the output will be 0. Electronic gates are implemented using transistors, and reconfiguring them (such as changing from an AND gate to a NOR gate) requires invasive modification, such as dismantling, which is usually too complicated to be practical.

“Reconfigurable gates, like the one we show, can behave as both types of logic gates, switching from AND to NOR and vice versa by changing only the gate voltage,” she continues. “Currently in electronics, functionality is defined by structure, but in our device you can change the behavior and make it something else just by changing the voltage applied to it. If we scale up this invention from a single gate to much more complex circuits consisting of many such reconfigurable gates, we can envision a powerful piece of hardware that can be programmed with many more functionalities than conventional ones having the same number of transistors.”

Another advantage to CPE-K-based OECTs: they can be operated at very low voltages, making them suitable for use in personal electronics. That, combined with its flexibility and bio-compatibility, make the material a likely candidate for implanted biosensors, wearable devices and neuromorphic computing systems in which OECTs might serve as artificial synapses or non-volatile memories.

“Our colleague is making devices that can monitor the drop of glucose level in the brain that occurs just before a seizure,” Nguyen explains of a collaborator at the University of Cambridge in England. “And after detection, another device — a microfluidic device — will deliver a drug locally to stop the process before it happens.”

Devices made from CPE-K feature concurrent doping and de-doping depending on the type of ions, according to Nguyen. “You make the device and put it in a liquid electrolyte — sodium chloride [i.e., table salt] dissolved in water,” she says. “You can then drive the sodium to migrate into the CPE-K active layer by applying a positive voltage at the gate. Alternatively, you can change the polarity of the gate voltage and drive chloride to migrate to the active layer. Each scenario produces a different type of ion injection, and those different ions are what allow us to change the modes of device operation.”

Self-doping also simplifies the manufacturing process by removing the extra step of adding dopants. “A lot of times when you add a dopant, it is not evenly distributed throughout the volume of the material,” Nguyen says. “The organic doping materials tend to cluster together instead of dispersing. But because our material doesn’t need that step, you don’t run into the issue of uneven dopant distribution. You also avoid the whole process of optimizing the dopant and determining the right mix and proportions, all of which add steps and complicate processing.”

The team also developed a physics model for the device that explains its working mechanism and correctly predicts its behavior in both operation modes, thus demonstrating that the device is doing what it seems to be doing.

Visell concludes, “This remarkable new transistor technology ideally exemplifies the surprising electronic and computing functionalities that are being enabled through convergent research in chemistry, physics, materials and electrical engineering.”

The newest paper from his research group examines the possibility of that technology. “Multiphoton Lithography of Organic Semiconductor Devices for 3D Printing of Flexible Electronic Circuits, Biosensors, and Bioelectronics” was published online in Advanced Materials.

Over the past few years, 3D printing of electronics have become a promising technology due to their potential applications in emerging fields such as nanoelectronics and nanophotonics. Among 3D microfabrication technologies, multiphoton lithography (MPL) is considered the state-of-the-art amongst the microfabrication methods with true 3D fabrication capability, excellent level of spatial and temporal control, and the versatility of photosensitive materials mostly composed of acrylate-based polymers/monomers or epoxy-based photoresists.

“In this paper we introduced a new photosensitive resin doped with an organic semiconductor material (OS) to fabricate highly conductive 3D microstructures with high-quality structural features via MPL process,” Abidian said.

They showed that the fabrication process could be performed on glass and flexible substrate poly(dimethylsilosane). They demonstrated that loading as low as 0.5 wt% OS into the resin remarkably increased electrical conductivity of printed organic semiconductor composite polymer over 10 orders of magnitude.

“The excellent electrical conductivity can be attributed to presence of OS in the cross-linked polymer chains, providing both ionic and electronic conduction pathways along the polymer chains,” Abidian said.

To demonstrate the potential electronic applications based on the OS composite resin, his team fabricated various microelectronic devices, including micro-printed circuit board, which comprises various electrical elements, and an array of microcapacitors.

Three dimensional bioprinting of organic semiconductor microdevices based on MPL has potential in biomedical applications including tissue engineering, bioelectronics and biosensors. Abidian’s team successfully incorporated bioactive molecules such as laminin and glucose oxidase into the OS composite microstructures (OSCMs). To confirm that the bioactivity of laminin was retained throughout the entire MPL process, primary mouse endothelial cells were cultured on OS composite microstructures. Cells seeded on laminin incorporated OSCMs displayed evidence of adherence to substrate, proliferation, and enhanced survival.

“We also assessed the biocompatibility of the OS composite structures by culturing lymphocytes, namely splenic T-cells and B-cells, on the fabricated surfaces and compared them with control surfaces. After seven days of culture, OS composite polymers did not induce cell mortality with approximately 94 percent cell viability compared to the control surfaces,” Abidian said. “In addition, the potential effect of OS composite polymers on cell activation was also studied. After seven days of culture, there was no significant difference in the expression of activation markers on the lymphocytes between OS composite structures and control surfaces.”

Finally, Abidian proposed a maskless method based on MPL for fabrication of bioelectronics and biosensors. They fabricated a glucose biosensor similar to Michigan style neural electrodes. Glucose oxidase, an enzyme for the specific recognition of glucose, was encapsulated within the solidified OS composite microelectrodes via the MPL process. The biosensor offered a highly sensitive glucose sensing platform with nearly 10-fold higher sensitivity compared to previous glucose biosensors. In addition, this biosensor exhibited excellent specificity and high reproducibility.

“We anticipate that the presented MPL-compatible OS composite resins will pave the path towards production of soft, bioactive, and conductive microstructures for various applications in the emerging fields of flexible bioelectronics, biosensors, nanoelectronics, organ-on-chips, and immune cell therapies.” Abidian said

Co-authors on the paper include former graduate students Omid Dadras-Toussi and Milad Khorrami; and postdoctoral researcher Anto Sam Crosslee Louis Sam Titus. Abidian praised the work of his students on this research and noted that Dadras-Toussi would be starting a new job with Medtronic, an S&P 100 company with $30 billion in yearly revenue, this month.

Sheereen Majd, associate professor of Biomedical Engineering, and Chandra Mohan, Hugh Roy and Lillie Cranz Cullen Endowed Professor of Biomedical Engineering at UH Cullen College of Engineering are also co-authors. Abidian said his colleagues were significant collaborators for the research.

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Materials provided by University of Houston. Original written by Stephen Greenwell. Note: Content may be edited for style and length.

Despite tremendous improvements in microscopy, there still exists a remarkable gap between resolution in all three dimensions. One of the methods that can close this gap and achieves a resolution in the nanometer range is metal-induced energy transfer (MIET) imaging. The exceptional depth resolution of MIET imaging was combined with the extraordinary lateral resolution of single-molecule localization microscopy, in particular with a method called direct stochastic optical reconstruction microscopy (dSTORM). The novel technique based on this combination allows researchers to achieve isotropic three-dimensional super-resolution imaging of sub-cellular structures. In addition, the researchers implement dual-color MIET-dSTORM enabling them to image two different cellular structures in three dimensions, for example microtubules and clathrin coated pits — tiny structures within cells — that exist together in the same area.

“By combining the established concepts, we developed a new technique for super-resolution microscopy. Its main advantage is it enables extremely high resolution in three dimensions, despite using a relatively simple setup,” says Dr Jan Christoph Thiele, first author of the publication, Göttingen University. “This will be a powerful tool with numerous applications to resolve protein complexes and small organelles with sub-nanometer accuracy. Everyone who has access to confocal microscope technology with a fast laser scanner and fluorescence lifetime measurements capabilities should try this technique,” says Dr Oleksii Nevskyi, one of the corresponding authors.

“The beauty of the technique is its simplicity. This means that researchers around the world will be able to implement the technology into their microscopes quickly,” adds Professor Jörg Enderlein who led the research team at the Biophysics Institute, Göttingen University. This method shows promise to become a powerful tool for multiplexed 3D super-resolution microscopy with extraordinary high resolution and a variety of applications in structural biology.

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