If you’re hoping for gold flecks in your glue, this is not going to satisfy you, given that it’s all at the nanoscale. An August 7, 2019 news item on Nanowerk briefly describes this gold glue (Note: A link has been removed),
It has long been known that gold can be used to do things that philosophers have never even dreamed of. The Institute of Nuclear Physics of the Polish Academy of Sciences in Cracow has confirmed the existence of ‘gold glue’: bonds involving gold atoms, capable of permanently bonding protein rings. Skilfully used by an international team of scientists, the bonds have made it possible to construct molecular nanocages with a structure so far unparalleled in nature or even in mathematics (Nature, “An ultra-stable gold-coordinated protein cage displaying reversible assembly”).
The world of science has been interested in molecular cages for years. Not without reason. Chemical molecules, including those that would under normal conditions enter into chemical reactions, can be enclosed within their empty interiors. The particles of the enclosed compound, separated by the walls of the cage from the environment, have nothing to bond with. These cages can be therefore be used, for example, to transport drugs safely into a cancer cell, only releasing the drug when they are inside it.
Molecular cages are polyhedra made up of smaller ‘bricks’, usually protein molecules. The bricks can’t be of any shape. For example, if we wanted to build a molecular polyhedron using only objects with the outline of an equilateral triangle, geometry would limit us to only three solid figures: a tetrahedron, an octahedron or an icosahedron. So far, there have been no other structural possibilities.
“Fortunately, Platonic idealism is not a dogma of the physical world. If you accept certain inaccuracies in the solid figure being constructed, you can create structures with shapes that are not found in nature, what’s more, with very interesting properties,” says Dr. Tomasz Wrobel from the Cracow Institute of Nuclear Physics of the Polish Academy of Sciences (IFJ PAN).
Dr. Wrobel is one of the members of an international team of researchers who have recently carried out the ‘impossible’: they built a cage similar in shape to a sphere out of eleven-walled proteins. The main authors of this spectacular success are scientists from the group of Prof. Jonathan Heddle from the Malopolska Biotechnology Centre of the Jagiellonian University in Cracow and the Japanese RIKEN Institute in Wako. The work described in Nature magazine took place with the participation of researchers from universities in Osaka and Tsukuba (Japan), Durham (Great Britain), Waterloo (Canada) and other research centres.
Each of the walls of the new nanocages was formed by a protein ring from which eleven cysteine molecules stuck out at regular intervals. It was to the sulphur atom found in each cysteine molecule that the ‘glue’, i.e. the gold atom, was planned to be attached. In the appropriate conditions, it could bind with one more sulphur atom, in the cysteine of a next ring. In this way a permanent chemical bond would be formed between the two rings. But would the gold atom under these conditions really be able to form a bond between the rings?
“In the Spectroscopic Imaging Laboratory of IFJ PAS we used Raman spectroscopy and X-ray photoelectron spectroscopy to show that in the samples provided to us with the test nanocages, the gold really did form bonds with sulphur atoms in cysteines. In other words, in a difficult, direct measurement, we proved that gold ‘glue’ for bonding protein rings in cages really does exist,” explains Dr. Wrobel.
Each gold atom can be treated as a stand-alone clip that makes it possible to attach another ring. The road to the ‘impossible’ begins when we realize that we don’t always have to use all of the clips! So, although all the rings of the new nanocages are physically the same, depending on their place in the structure they connect with their neighbours with a different number of gold atoms, and thus function as polygons with different numbers of vertices. 24 nanocage walls presented by the researchers were held together by 120 gold atoms. The outer diameter of the cages was 22 nanometres and the inner diameter was 16 nm.
Using gold atoms as a binder for nanocages is also important due to its possible applications. In earlier molecular structures, proteins were glued together using many weak chemical bonds. The complexity of the bonds and their similarity to the bonds responsible for the existence of the protein rings themselves did not allow for precise control over the decomposition of the cages. This is not the case in the new structures. On the one hand, gold-bonded nanocages are chemically and thermally stable (for example, they withstand hours of boiling in water). On the other hand, however, gold bonds are sensitive to an increase in acidity. By its increase, the nanocage can be decomposed in a controlled way and the contents can be released into the environment. Since the acidity within cells is greater than outside them, gold-bonded nanocages are ideal for biomedical applications.
The ‘impossible’ nanocage is the presentation of a qualitatively new approach to the construction of molecular cages, with gold atoms in the role of loose clips. The demonstrated flexibility of the gold bonds will make it possible in the future to create nanocages with sizes and features precisely tailored to specific needs.
Here’s a link to and a citation for the paper.
An ultra-stable gold-coordinated protein cage displaying reversible assembly by Ali D. Malay, Naoyuki Miyazaki, Artur Biela, Soumyananda Chakraborti, Karolina Majsterkiewicz, Izabela Stupka, Craig S. Kaplan, Agnieszka Kowalczyk, Bernard M. A. G. Piette, Georg K. A. Hochberg, Di Wu, Tomasz P. Wrobel, Adam Fineberg, Manish S. Kushwah, Mitja Kelemen, Primož Vavpetič, Primož Pelicon, Philipp Kukura, Justin L. P. Benesch, Kenji Iwasaki & Jonathan G. Heddle Nature volume 569, pages438–442 (2019) Issue Date: 16 May 2019 DOI: https://doi.org/10.1038/s41586-019-1185-4 Published online: 08 May 2019
An August 5, 2019 news item on Nanowerk announces a new technology for detecting killer bacteria (Note: A link has been removed),
A combination of off-the-shelf quantum dots and a smartphone camera soon could allow doctors to identify antibiotic-resistant bacteria in just 40 minutes, potentially saving patient lives.
Staphylococcus aureus (golden staph), is a common form of bacterium that causes serious and sometimes fatal conditions such as pneumonia and heart valve infections. Of particular concern is a strain that does not respond to methicillin, the antibiotic of first resort, and is known as methicillin-resistant S. aureus, or MRSA.
Recent reports estimate that 700 000 deaths globally could be attributed to antimicrobial resistance, such as methicillin-resistance. Rapid identification of MRSA is essential for effective treatment, but current methods make it a challenging process, even within well-equipped hospitals.
Soon, however, that may change, using nothing except existing technology.
Researchers from Macquarie University and the University of New South Wales, both in Australia, have demonstrated a proof-of-concept device that uses bacterial DNA to identify the presence of Staphylococcus aureus positively in a patient sample – and to determine if it will respond to frontline antibiotics.
In a paper published in the international peer-reviewed journal Sensors and Actuators B: Chemical the Macquarie University team of Dr Vinoth Kumar Rajendran, Professor Peter Bergquist and Associate Professor Anwar Sunna with Dr Padmavathy Bakthavathsalam (UNSW) reveal a new way to confirm the presence of the bacterium, using a mobile phone and some ultra-tiny semiconductor particles known as quantum dots.
“Our team is using Synthetic Biology and NanoBiotechnology to address biomedical challenges. Rapid and simple ways of identifying the cause of infections and starting appropriate treatments are critical for treating patients effectively,” says Associate Professor Anwar Sunna, head of the Sunna Lab at Macquarie University.
“This is true in routine clinical situations, but also in the emerging field of personalised medicine.”
The researchers’ approach identifies the specific strain of golden staph by using a method called convective polymerase chain reaction (or cPCR). This is a derivative of a widely -employed technique in which a small segment of DNA is copied thousands of times, creating multiple samples suitable for testing.
Vinoth Kumar and colleagues then subject the DNA copies to a process known as lateral flow immunoassay – a paper-based diagnostic tool used to confirm the presence or absence of a target biomarker. The researchers use probes fitted with quantum dots to detect two unique genes, that confirms the presence of methicillin resistance in golden staph
A chemical added at the PCR stage to the DNA tested makes the sample fluoresce when the genes are detected by the quantum dots – a reaction that can be captured easily using the camera on a mobile phone.
The result is a simple and rapid method of detecting the presence of the bacterium, while simultaneously ruling first-line treatment in or out.
Although currently at proof-of-concept stage, the researchers say their system which is powered by a simple battery is suitable for rapid detection in different settings.
“We can see this being used easily not only in hospitals, but also in GP clinics and at patient bedsides,” says lead author, Macquarie’s Vinoth Kumar Rajendran.
If I understand this research rightly, they are creating a film made of carbon nanotubes that can stimulate the growth of nerve cells (neurons) thus creating a ‘living/nonliving’ hybrid or as they call it in the press release a ‘biosynthetic hybrid’.
An August 2, 2019 news item on Nanowerk introduces the research (Note 1: There seem to be some translation issues; Note 2: Links have been removed),
Carbon nanotubes able to take on the desired shapes thanks to a special chemical treatment, called crosslinking and, at the same time, able to function as substrata for the growth of nerve cells, finely tuning their growth and activity.
The research published in ACS Nano (“Chemically Cross-Linked Carbon Nanotube Films Engineered to Control Neuronal Signaling”), is a new and important step towards the construction of neuronal regenerative-interfaces to repair spinal injuries.
The study is the new achievement of a long-term and, in terms of results, successful collaboration between the scientists Laura Ballerini of SISSA (Scuola Internazionale Superiore di Studi Avanzati), Trieste, and Maurizio Prato of the University of Trieste. The work team has also been assisted by CIC biomaGUNE of San Sebastián, Spain.
The carbon nanotubes used in the research have been modified by appropriate chemical treatments: “For many years, in our laboratories we have been working on the chemical reactivity of carbon nanotubes, a fascinating but very difficult material to work. Thanks to our experience, we have crosslinked them or, to say it more clearly, we have treated the nanotubes so they could link themselves to one another thanks to specific chemical reactions. We have discovered that this procedure gives the material very interesting characteristics. For example, the material organises itself in a stable manner according to a precise shape, we choose: a tissue where nerve cells need to be planted, for example. Or around some electrodes” explains Professor Prato. “We know from previous research that nerve cells grow well on carbon nanotubes so they could be used as a surface to build hybrid devices to regenerate nerve tissues. It was necessary to ensure that this chemical modification did not compromise this process and study whether the interaction with neurons was altered”.
Towards biosynthetic hybrids
Professor Ballerini continues: “We have discovered that the chemical process has important effects because through this treatment we can modulate the activity of neurons, in terms of growth, adhesion and survival. These materials can also regulate the communication between neurons. We can say that the carpet of crosslinked carbon nanotubes interacts intensely and constructively with the nerve cells”. This interaction depends on how much the different carbon nanotubes are linked to each other, or rather crosslinked. The lower the link number among the nanotubes the higher the activity of neurons that grow on their surface. Through the chemical control of their properties, and of the links between them, it is possible to regulate the response of the neurons. Ballerini and Prato explain: “This is an intriguing result that emerges from the important and fruitful collaboration between our research groups involving advanced research in chemistry, nanoscience and neurobiology . This study provides a further step in the design of future biosynthetic hybrids to recover injured nerve tissues functions”.
An August 2, 2019 news item on ScienceDaily features some new work on wearable technology that was a bit of a surprise to me,
Wearable human-machine interfaces — devices that can collect and store important health information about the wearer, among other uses — have benefited from advances in electronics, materials and mechanical designs. But current models still can be bulky and uncomfortable, and they can’t always handle multiple functions at one time.
Researchers reported Friday, Aug. 2 , the discovery of a multifunctional ultra-thin wearable electronic device that is imperceptible to the wearer.
I expected this wearable technology to be a piece of clothing that somehow captured health data but it’s not,
The device allows the wearer to move naturally and is less noticeable than wearing a Band-Aid, said Cunjiang Yu, Bill D. Cook Associate Professor of Mechanical Engineering at the University of Houston and lead author for the paper, published as the cover story in Science Advances.
“Everything is very thin, just a few microns thick,” said Yu, who also is a principal investigator at the Texas Center for Superconductivity at UH. “You will not be able to feel it.” It has the potential to work as a prosthetic skin for a robotic hand or other robotic devices, with a robust human-machine interface that allows it to automatically collect information and relay it back to the wearer.
That has applications for health care – “What if when you shook hands with a robotic hand, it was able to instantly deduce physical condition?” Yu asked – as well as for situations such as chemical spills, which are risky for humans but require human decision-making based on physical inspection.
While current devices are gaining in popularity, the researchers said they can be bulky to wear, offer slow response times and suffer a drop in performance over time. More flexible versions are unable to provide multiple functions at once – sensing, switching, stimulation and data storage, for example – and are generally expensive and complicated to manufacture.
The device described in the paper, a metal oxide semiconductor on a polymer base, offers manufacturing advantages and can be processed at temperatures lower than 300 C.
“We report an ultrathin, mechanically imperceptible, and stretchable (human-machine interface) HMI device, which is worn on human skin to capture multiple physical data and also on a robot to offer intelligent feedback, forming a closed-loop HMI,” the researchers wrote. “The multifunctional soft stretchy HMI device is based on a one-step formed, sol-gel-on-polymer-processed indium zinc oxide semiconductor nanomembrane electronics.”
In addition to Yu, the paper’s co-authors include first author Kyoseung Sim, Zhoulyu Rao, Faheem Ershad, Jianming Lei, Anish Thukral and Jie Chen, all of UH; Zhanan Zou and Jianliang Xiao, both of the University of Colorado; and Qing-An Huang of Southeast University in Nanjing, China.
The gold sheets in question are effectively 2D. I’m surprised they haven’t named them ‘goldene’ as everything else that’s 2D seems to have an ‘ene’ suffix (e.g. graphene, germanene, tellurene).
Of course, these gold sheets are not composed of single atoms but of two according to an August 6, 2019 news item on Nanowerk,
Scientists at the University of Leeds [UK] have created a new form of gold which is just two atoms thick – the thinnest unsupported gold ever created.
The researchers measured the thickness of the gold to be 0.47 nanometres – that is one million times thinner than a human finger nail. The material is regarded as 2D because it comprises just two layers of atoms sitting on top of one another. All atoms are surface atoms – there are no ‘bulk’ atoms hidden beneath the surface.
I’m pretty sure they’ve added colour to those images and not just in the background; they’ve likely added a gold colour to the gold.
The material could have wide-scale applications in the medical device and electronics industries – and also as a catalyst to speed up chemical reactions in a range of industrial processes.
Laboratory tests show that the ultra-thin gold is 10 times more efficient as a catalytic substrate than the currently used gold nanoparticles, which are 3D materials with the majority of atoms residing in the bulk rather than at the surface.
Scientists believe the new material could also form the basis of artificial enzymes that could be applied in rapid, point-of-care medical diagnostic tests and in water purification systems.
The announcement that the ultra-thin metal had been successfully synthesised was made in the journal Advanced Science.
The lead author of the paper, Dr Sunjie Ye, from Leeds’ Molecular and Nanoscale Physics Group and the Leeds Institute of Medical Research, said: “This work amounts to a landmark achievement.
“Not only does it open up the possibility that gold can be used more efficiently in existing technologies, it is providing a route which would allow material scientists to develop other 2D metals.
“This method could innovate nanomaterial manufacturing.”
The research team are looking to work with industry on ways of scaling-up the process.
Synthesising the gold nanosheet takes place in an aqueous solution and starts with chloroauric acid, an inorganic substance that contains gold. It is reduced to its metallic form in the presence of a ‘confinement agent’ – a chemical that encourages the gold to form as a sheet, just two atoms thick.
Because of the gold’s nanoscale dimensions, it appears green in water – and given its shape, the researchers describe it as gold nanoseaweed.
Professor Stephen Evans, head of the Leeds’ Molecular and Nanoscale Research Group who supervised the research, said the considerable gains that could be achieved from using these ultra-thin gold sheets are down to their high surface-area to volume ratio.
He said: “Gold is a highly effective catalyst. Because the nanosheets are so thin, just about every gold atom plays a part in the catalysis. It means the process is highly efficient.”
Standard benchmark tests revealed that gold nanoscale sheets were ten times more efficient than the gold nanoparticles conventionally used in industry.
Professor Evans said: “Our data suggests that industry could get the same effect from using a smaller amount of gold, and this has economic advantages when you are talking about a precious metal.”
Similar benchmark tests revealed that the gold sheets could act as highly effective artificial enzymes.
The flakes are also flexible, meaning they could form the basis of electronic components for bendable screens, electronic inks and transparent conducting displays.
Professor Evans thinks there will inevitably be comparisons made between the 2D gold and the very first 2D material ever created – graphene, which was fabricated at the University of Manchester in 2004.
He said: “The translation of any new material into working products can take a long time and you can’t force it to do everything you might like to. With graphene, people have thought that it could be good for electronics or for transparent coatings – or as carbon nanotubes that could make an elevator to take us into space because of its super strength.
“I think with 2D gold we have got some very definite ideas about where it could be used, particularly in catalytic reactions and enzymatic reactions. We know it will be more effective than existing technologies – so we have something that we believe people will be interested in developing with us.”
Here’s a link to and a citation for the paper,
Sub‐Nanometer Thick Gold Nanosheets as Highly Efficient Catalysts by Sunjie Ye, Andy P. Brown, Ashley C. Stammers, Neil H. Thomson, Jin Wen, Lucien Roach, Richard J. Bushby, Patricia Louise Coletta, Kevin Critchley, Simon D. Connell, Alexander F. Markham, Rik Brydson, Stephen D. Evans. Advnaced Science https://doi.org/10.1002/advs.201900911 First published: 06 August 2019
Scientists at Northwestern University (Chicago, Illinois) and the California Institute of Technology (CalTech) have developed what could be a more sustainable way to produce electricity. From a July 31, 2019 news item on Nanowerk,
Scientists from Northwestern University and Caltech have produced electricity by simply flowing water over extremely thin layers of inexpensive metals, including iron, that have oxidized. These films represent an entirely new way of generating electricity and could be used to develop new forms of sustainable power production.
The films have a conducting metal nanolayer (10 to 20 nanometers thick) that is insulated with an oxide layer (2 nanometers thick). Current is generated when pulses of rainwater and ocean water alternate and move across the nanolayers. The difference in salinity drags the electrons along in the metal below.
“It’s the oxide layer over the nanometal that really makes this device go,” said Franz M. Geiger, the Dow Professor of Chemistry in Northwestern’s Weinberg College of Arts and Sciences. “Instead of corrosion, the presence of the oxides on the right metals leads to a mechanism that shuttles electrons.”
The films are transparent, a feature that could be taken advantage of in solar cells. The researchers intend to study the method using other ionic liquids, including blood. Developments in this area could lead to use in stents and other implantable devices.
“The ease of scaling up the metal nanolayer to large areas and the ease with which plastics can be coated gets us to three-dimensional structures where large volumes of liquids can be used,” Geiger said. “Foldable designs that fit, for instance, into a backpack are a possibility as well. Given how transparent the films are, it’s exciting to think about coupling the metal nanolayers to a solar cell or coating the outside of building windows with metal nanolayers to obtain energy when it rains.”
The study, titled “Energy Conversion via Metal Nanolayers,” was published this week [on July 29, 2019] in the journal Proceedings of the National Academy of Sciences (PNAS).
Geiger is the study’s corresponding author; his Northwestern team conducted the experiments. Co-author Thomas Miller, professor of chemistry at Caltech, led a team that conducted atomistic simulations to study the device’s behavior at the atomic level.
The new method produces voltages and currents comparable to graphene-based devices reported to have efficiencies of around 30% — similar to other approaches under investigation (carbon nanotubes and graphene) but with a single-step fabrication from earth-abundant elements instead of multistep fabrication. This simplicity allows for scalability, rapid implementation and low cost. Northwestern has filed for a provisional patent.
Of the metals studied, the researchers found that iron, nickel and vanadium worked best. They tested a pure rust sample as a control experiment; it did not produce a current.
The mechanism behind the electricity generation is complex, involving ion adsorption and desorption, but it essentially works like this: The ions present in the rainwater/saltwater attract electrons in the metal beneath the oxide layer; as the water flows, so do those ions, and through that attractive force, they drag the electrons in the metal along with them, generating an electrical current.
“There are interesting prospects for a variety of energy and sustainability applications, but the real value is the new mechanism of oxide-metal electron transfer,” Geiger said. “The underlying mechanism appears to involve various oxidation states.”
The team used a process called physical vapor deposition (PVD), which turns normally solid materials into a vapor that condenses on a desired surface. PVD allowed them to deposit onto glass metal layers only 10 to 20 nanometers thick. An oxide layer then forms spontaneously in air. It grows to a thickness of 2 nanometers and then stops growing.
“Thicker films of metal don’t succeed — it’s a nano-confinement effect,” Geiger said. “We have discovered the sweet spot.”
When tested, the devices generated several tens of millivolts and several microamps per centimeter squared.
“For perspective, plates having an area of 10 square meters each would generate a few kilowatts per hour — enough for a standard U.S. home,” Miller said. “Of course, less demanding applications, including low-power devices in remote locations, are more promising in the near term.”
Here’s a link to and a citation for the paper,
Energy conversion via metal nanolayers by Mavis D. Boamah, Emilie H. Lozier, Jeongmin Kim, Paul E. Ohno, Catherine E. Walker, Thomas F. Miller III, and Franz M. Geiger. PNAS DOI: https://doi.org/10.1073/pnas.1906601116 First published July 29, 2019
If successful the hope is that ‘human-on-a-chip’ will replace most, if not all, animal testing. This July 3, 2019 Hesperos news release (also on EurekAlert) suggests scientists are making serious gains in the drive to replace animal testing (Note: For anyone having difficulty with the terms, pharmacokinetics and pharmacodynamics, there are definitions towards the end of this posting, which may prove helpful),
Hesperos Inc., pioneers* of the “human-on-a-chip” in vitro system has announced the use of its innovative multi-organ model to successfully measure the concentration and metabolism of two known cardiotoxic small molecules over time, to accurately describe the drug behavior and toxic effects in vivo. The findings further support the potential of body-on-a-chip systems to transform the drug discovery process.
In a study published in Nature Scientific Reports, in collaboration with AstraZeneca, Hesperos described how they used a pumpless heart model and a heart:liver system to evaluate the temporal pharmacokinetic/pharmacodynamic (PKPD) relationship for terfenadine, an antihistamine that was banned due to toxic cardiac effects, as well as determine its mechanism of toxicity.
The study found there was a time-dependent, drug-induced response in the heart model. Further experiments were conducted, adding a metabolically competent liver module to the Hesperos Human-on-a-Chip® system to observe what happened when terfenadine was converted to fexofenadine. By doing so, the researchers were able to determine the driver of the pharmacodynamic (PD) effect and develop a mathematical model to predict the effect of terfenadine in preclinical species. This is the first time an in vitro human-on-a-chip system has been shown to predict in vivo outcomes, which could be used to predict clinical trial outcomes in the future.
“The ability to examine PKPD relationships in vitro would enable us to understand compound behavior prior to in vivo testing, offering significant cost and time savings,” said Dr. Shuler, President and CEO, Hesperos, Inc and Professor Emeritus, Cornell University. “We are excited about the potential of this technology to help us ensure that potential new drug candidates have a higher probability of success during the clinical trial process.”
Understanding the inter-relationship between pharmacokinetics (PK), the drug’s time course for absorption, distribution, metabolism and excretion, and PD, the biological effect of a drug, is crucial in drug discovery and development. Scientists have learned that the maximum drug effect is not always driven by the peak drug concentration. In some cases, time is a critical factor influencing drug effect, but often this concentration-effect-time relationship only comes to light during the advanced stages of the preclinical program. In addition, often the data cannot be reliably extrapolated to humans.
“It is costly and time consuming to discover that potential drug candidates may have poor therapeutic qualities preventing their onward progression,” said James Hickman, Chief Scientist at Hesperos and Professor at the University of Central Florida. “Being able to define this during early drug discovery will be a valuable contribution to the optimization of potential new drug candidates.”
As demonstrated with the terfenadine experiment, the PKPD modelling approach was critical for understanding both the flux of compound between compartments as well as the resulting PD response in the context of dynamic exposure profiles of both parent and metabolite, as indicated by Dr. Shuler.
In order to test the viability of their system in a real-world drug discovery setting, the Hesperos team collaborated with scientists at AstraZeneca, to test one of their failed small molecules, known to have a CV [cardiovscular?] risk.
One of the main measurements used to assess the electrical properties of the heart is the QT interval, which approximates the time taken from when the cardiac ventricles start to contract to when they finish relaxing. Prolongation of the QT interval on the electrocardiogram can lead to a fatal arrhythmia known as Torsade de Pointes. Consequently, it is a mandatory requirement prior to first-in-human administration of potential new drug candidates that their ability to inhibit the hERG channel (a biomarker for QT prolongation) is investigated.
In the case of the AstraZeneca molecule, the molecule was assessed for hERG inhibition early on, and it was concluded to have a low potential to cause in vivo QT prolongation up to 100 μM. In later pre-clinical testing, the QT interval increased by 22% at a concentration of just 3 μM. Subsequent investigations found that a major metabolite was responsible. Hesperos was able to detect a clear PD effect at concentrations above 3 μM and worked to determine the mechanism of toxicity of the molecule.
The ability of these systems to assess cardiac function non-invasively in the presence of both parent molecule and metabolite over time, using multiplexed and repeat drug dosing regimes, provides an opportunity to run long-term studies for chronic administration of drugs to study their potential toxic effects.
Hesperos, Inc. is the first company spun out from the Tissue Chip Program at NCATS (National Center for Advancing Translational Sciences), which was established in 2011 to address the long timelines, steep costs and high failure rates associated with the drug development process. Hesperos currently is funded through NCATS’ Small Business Innovation Research program to undertake these studies and make tissue chips technology available as a service based company.
“The application of tissue chip technology in drug testing can lead to advances in predicting the potential effects of candidate medicines in people,” said Danilo Tagle, Ph.D., associate director for special initiatives at NCATS.
About Hesperos Hesperos, Inc. is a leader in efforts to characterize an individual’s biology with human-on-a-chip microfluidic systems. Founders Michael L. Shuler and James J. Hickman have been at the forefront of every major scientific discovery in this realm, from individual organ-on-a-chip constructs to fully functional, interconnected multi-organ systems. With a mission to revolutionize toxicology testing as well as efficacy evaluation for drug discovery, the company has created pumpless platforms with serum-free cellular mediums that allow multi-organ system communication and integrated computational PKPD modeling of live physiological responses utilizing functional readouts from neurons, cardiac, muscle, barrier tissues and neuromuscular junctions as well as responses from liver, pancreas and barrier tissues. Created from human stem cells, the fully human systems are the first in vitro solutions that accurately utilize in vitro systems to predict in vivo functions without the use of animal models, as featured in Science. More information is available at http://www. hesperosinc.com
Years ago I went to a congress focused on alternatives to animal testing (August 22, 2014 posting) and saw a video of heart cells in a petri dish (in vitro) beating in a heartlike rhythm. It was something like this,
ipscira Published on Oct 17, 2010 https://www.youtube.com/watch?v=BqzW9Jq-OVA
I found it amazing as did the scientist who drew my attention to it. After, it’s just a collection of heart cells. How do they start beating and keep time with each other?
Getting back to the latest research, here’s a link and a citation for the paper,
On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships by Christopher W. McAleer, Amy Pointon, Christopher J. Long, Rocky L. Brighton, Benjamin D. Wilkin, L. Richard Bridges, Narasimham Narasimhan Sriram, Kristin Fabre, Robin McDougall, Victorine P. Muse, Jerome T. Mettetal, Abhishek Srivastava, Dominic Williams, Mark T. Schnepper, Jeff L. Roles, Michael L. Shuler, James J. Hickman & Lorna Ewart. Scientific Reports volume 9, Article number: 9619 (2019) DOI: https://doi.org/10.1038/s41598-019-45656-4 Published: 03 July 2019
Integrative pharmacology is a discipline that builds an understanding of the inter-relationship between pharmacokinetics (PK), the drug’s time course for absorption, distribution, metabolism and excretion and pharmacodynamics (PD), the biological effect of a drug. In drug discovery, this multi-variate approach guides medicinal chemists to modify structural properties of a drug molecule to improve its chance of becoming a medicine in a process known as “lead optimization”.
*More than one person and more than one company and more than one country claims pioneer status where ‘human-on-a-chip’ is concerned.
I’m getting to the science but first this video of what looks like jiggling jello,
In actuality, it’s a superhydrophobic coating demonstration and a July 2, 2019 news item on phys.org provides more information,
Plant leaves have a natural superpower—they’re designed with water repelling characteristics. Called a superhydrophobic surface, this trait allows leaves to cleanse themselves from dust particles. Inspired by such natural designs, a team of researchers at Texas A&M University has developed an innovative way to control the hydrophobicity of a surface to benefit to the biomedical field.
Researchers in Dr. Akhilesh K. Gaharwar’s lab in the Department of Biomedical Engineering have developed a “lotus effect” by incorporating atomic defects in nanomaterials, which could have widespread applications in the biomedical field including biosensing, lab-on-a-chip, blood-repellent, anti-fouling and self-cleaning applications.
Superhydrophobic materials are used extensively for self-cleaning characteristic of devices. However, current materials require alteration to the chemistry or topography of the surface to work. This limits the use of superhydrophobic materials.
“Designing hydrophobic surfaces and controlling the wetting behavior has long been of great interest, as it plays crucial role in accomplishing self-cleaning ability,” Gaharwar said. “However, there are limited biocompatible approach to control the wetting behavior of the surface as desired in several biomedical and biotechnological applications.”
The Texas A&M design adopts a ‘nanoflower-like’ assembly of two-dimensional (2D) atomic layers to protect the surface from wetting. The team recently released a study published in Chemical Communications. 2D nanomaterials are an ultrathin class of nanomaterials and have received considerable attention in research. Gaharwar’s lab used 2D molybdenum disulfide (MoS2), a new class of 2D nanomaterials that has shown enormous potential in nanoelectronics, optical sensors, renewable energy sources, catalysis and lubrication, but has not been investigated for biomedical applications. This innovative approach demonstrates applications of this unique class of materials to the biomedical industry.
“These 2D nanomaterials with their hexagonal packed layer repel water adherence, however, a missing atom from the top layer can allow easy access to water molecules by the next layer of atoms underneath making it transit from hydrophobic to hydrophilic,” said lead author of the study, Dr. Manish Jaiswal, a senior research associate in Gaharwar’s lab.
This innovative technique opens many doors for expanded applications in several scientific and technological areas. The superhydrophobic coating can be easily applied over various substrates such as glass, tissue paper, rubber or silica using the solvent evaporation method. These superhydrophobic coatings have wide-spread applications, not only in developing self-cleaning surfaces in nanoelectronics devices, but also for biomedical applications.
Specifically, the study demonstrated that blood and cell culture media containing proteins do not adhere to the surface, which is very promising. In addition, the team is currently exploring the potential applications of controlled hydrophobicity in stem cell fate.
We’re back on the cyborg trail or what I sometimes refer to as machine/flesh. A July 3, 2019 news item on ScienceDaily describes the latest attempts to join machine with flesh,
Machine enhanced humans — or cyborgs as they are known in science fiction — could be one step closer to becoming a reality, thanks to new research Lieber Group at Harvard University, as well as scientists from University of Surrey and Yonsei University.
Researchers have conquered the monumental task of manufacturing scalable nanoprobe arrays small enough to record the inner workings of human cardiac cells and primary neurons.
The ability to read electrical activities from cells is the foundation of many biomedical procedures, such as brain activity mapping and neural prosthetics. Developing new tools for intracellular electrophysiology (the electric current running within cells) that push the limits of what is physically possible (spatiotemporal resolution) while reducing invasiveness could provide a deeper understanding of electrogenic cells and their networks in tissues, as well as new directions for human-machine interfaces.
The Lieber Group at Harvard University provided this image illustrating the work,
In a paper published by Nature Nanotechnology, scientists from Surrey’s Advanced Technology Institute (ATI) and Harvard University detail how they produced an array of the ultra-small U-shaped nanowire field-effect transistor probes for intracellular recording. This incredibly small structure was used to record, with great clarity, the inner activity of primary neurons and other electrogenic cells, and the device has the capacity for multi-channel recordings.
Dr Yunlong Zhao from the ATI at the University of Surrey said: “If our medical professionals are to continue to understand our physical condition better and help us live longer, it is important that we continue to push the boundaries of modern science in order to give them the best possible tools to do their jobs. For this to be possible, an intersection between humans and machines is inevitable.
“Our ultra-small, flexible, nanowire probes could be a very powerful tool as they can measure intracellular signals with amplitudes comparable with those measured with patch clamp techniques; with the advantage of the device being scalable, it causes less discomfort and no fatal damage to the cell (cytosol dilation). Through this work, we found clear evidence for how both size and curvature affect device internalisation and intracellular recording signal.”
Professor Charles Lieber from the Department of Chemistry and Chemical Biology at Harvard University said: “This work represents a major step towards tackling the general problem of integrating ‘synthesised’ nanoscale building blocks into chip and wafer scale arrays, and thereby allowing us to address the long-standing challenge of scalable intracellular recording.
“The beauty of science to many, ourselves included, is having such challenges to drive hypotheses and future work. In the longer term, we see these probe developments adding to our capabilities that ultimately drive advanced high-resolution brain-machine interfaces and perhaps eventually bringing cyborgs to reality.”
Professor Ravi Silva, Director of the ATI at the University of Surrey, said: “This incredibly exciting and ambitious piece of work illustrates the value of academic collaboration. Along with the possibility of upgrading the tools we use to monitor cells, this work has laid the foundations for machine and human interfaces that could improve lives across the world.”
Dr Yunlong Zhao and his team are currently working on novel energy storage devices, electrochemical probing, bioelectronic devices, sensors and 3D soft electronic systems. Undergraduate, graduate and postdoc students with backgrounds in energy storage, electrochemistry, nanofabrication, bioelectronics, tissue engineering are very welcome to contact Dr Zhao to explore the opportunities further.
This time it’s the performing arts. I have one theatre and psychiatry production in Toronto and a music and medical science event in Vancouver.
Toronto’s Here are the Fragments opening on November 19, 2019
From a November 2, 2019 ArtSci Salon announcement (received via email),
An immersive theatre experience inspired by the psychiatric writing of Frantz Fanon
Here are the Fragments. Co-produced by The ECT Collective and The Theatre Centre November 19-December 1, 2019 Tickets: Preview $17 | Student/senior/arts worker $22 | Adult $30 Service charges may apply Book 416-538-0988 | PURCHASE ONLINE
An immigrant psychiatrist develops psychosis and then schizophrenia. He walks a long path towards reconnection with himself, his son, and humanity.
Walk with him.
Within our immersive design (a fabric of sound, video, and live actors) lean in close to the possibilities of perceptual experience.
Schizophrenics ‘hear voices’. Schizophrenics fear loss of control over their own thoughts and bodies. But how does any one of us actually separate internal and external voices? How do we trust what we see or feel? How do we know which voices are truly our own?
Within the installation find places of retreat from chaos. Find poetry. Find critical analysis.
Explore archival material, Fanon’s writings and contemporary interviews with psychiatrists, neuroscientists, artists, and people living with schizophrenia, to reflect on the relationships between identity, history, racism and mental health.
How do we trust what we see or feel? How do we know which voices are truly our own? THE THEATRE CENTRE and THE ECT COLLECTIVE are proud to Co-produce HERE ARE THE FRAGMENTS., an immersive work of theatre written by Suvendrini Lena, Theatre Centre Residency artist and CAMH [ Centre for Addiction and Mental Health] Neurologist. Based on the psychiatric writing of famed political theorist Frantz Fanon and combining narratives, sensory exploration, and scientific and historical analysis, HERE ARE THE FRAGMENTS. reflects on the relationships between identity, history, racism, and mental health. FRAGMENTS. will run November 19 to December 1 at The Theatre Centre (Opening Night November 21).
HERE ARE THE FRAGMENTS. consists of live performances within an interactive installation. The plot, told in fragments, follows a psychiatrist early in his training as he develops psychosis and ultimately, treatment resistant schizophrenia. Eduard, his son, struggles to connect with his father, while the young man must also make difficult treatment decisions.
The Theatre Centre’s Franco Boni Theatre and Gallery will be transformed into an immersive interactive installation. The design will offer many spaces for exploration, investigation, and discovery, bringing audiences into the perceptual experience of Schizophrenia. The scenes unfold around you, incorporating a fabric of sound, video, and live actors. Amidst the seeming chaos there will also be areas of retreat; whispering voices, Fanon’s own books, archival materials, interviews with psychiatrists, neuroscientists, and people living with schizophrenia all merge to provoke analysis and reflection on the intersection of racism and mental health.
Suvendrini Lena (Writer) is a playwright and neurologist. She works as the staff neurologist at the Centre for Addiction and Mental Health and at the Centre for Headache at Women’s College Hospital [Toronto]. She is an Assistant Professor of Psychiatry and Neurology at the University of Toronto where she teaches medical students, residents, and fellows. She also teaches a course called Staging Medicine, a collaboration between The Theatre Centre and University of Toronto Postgraduate Medical Education.
Frantz Fanon (1925-1961), was a French West Indian psychiatrist, political philosopher, revolutionary, and writer, whose works are influential in the fields of post-colonial studies, critical theory, and Marxism. Fanon published numerous books, including Black Skin, White Masks (1952) and The Wretched of the Earth (1961).
In addition to performances, The Theatre Centre will host a number of panels and events. Highlights include a post-show talkback with Ngozi Paul (Development Producer, Artist/Activist) and Psychiatrist Collaborator Araba Chintoh on November 22. Also of note is Our Patients and Our Selves: Experiences of Racism Among Health Care Workers with facilitator Dr. Fatimah Jackson-Best of Black Health Alliance on November 23rd and Fanon Today: A Creative Symposium on November 24th, a panel, reading, and creative discussion featuring David Austin, Frank Francis, Doris Rajan and George Elliot Clarke [formerly Toronto’s Poet Laureate and Canadian Parliamentary Poet Laureate; emphasis and link mine].
Sounds and Science: Vienna meets Vancouver on November 30, 2019
‘Sounds and Science’ originated at the Medical University of Vienna (Austria) as the November 6, 2019 event posting on the University of British Columbia’s (UBC) Faculty of Medicine website,
The University of British Columbia will host the first Canadian concert bringing leading musical talents of Vienna together with dramatic narratives from science and medicine.
“Sounds and Science: Vienna Meets Vancouver” is part of the President’s Concert Series, to be held Nov. 30, 2019 on UBC campus. The event is modeled on a successful concert series launched in Austria in 2014, in cooperation with the Medical University of Vienna.
“Basic research tends to always stay within its own box, yet research is telling the most beautiful stories,” says Dr. Josef Penninger, director of UBC’s Life Sciences Institute, a professor of medical genetics and a Canada 150 Chair. “With this concert, we are bringing science out of the ivory tower, using the music of great composers such as Mozart, Schubert or Strauss to transport stories of discovery and insight into the major diseases that affected the composers themselves, and continue to have a significant impact on our society.”
Famous composers of the past are often seen as icons of classical music, but in fact, they were human beings, living under enormous physical constraints – perhaps more than people today, according to Dr. Manfred Hecking, an associate professor of internal medicine at the Medical University of Vienna.
“But ‘Sounds and Science’ is not primarily about suffering and disease,” says Dr. Hecking, a former member of the Vienna Philharmonic Orchestra who will be playing double bass during the concert. “It is a fun way of bringing music and science together. Combining music and thought, we hope that we will reach the attendees of the ‘Sounds and Science’ concert in Vancouver on an emotional, perhaps even personal level.”
A showcase for Viennese music, played in the tradition of the Vienna Philharmonic by several of its members, as well as the world-class science being done here at UBC, “Sounds and Science” will feature talks by UBC clinical and research faculty, including Dr. Penninger. Their topics will range from healthy aging and cancer research to the historical impact of bacterial infections.
Combining music and thought, we hope that we will reach the attendees of the ‘Sounds and Science’ concert in Vancouver on an emotional, perhaps even personal level. Dr. Manfred Hecking
Faculty speaking at “Sounds and Science” will be: Dr. Allison Eddy, professor and head, department of pediatrics, and chief, pediatric medicine, BC Children’s Hospital and BC Women’s Hospital; Dr. Troy Grennan, clinical assistant professor, division of infectious diseases, UBC faculty of medicine; Dr. Poul Sorensen, professor, department of pathology and laboratory medicine, UBC faculty of medicine; and Dr. Roger Wong, executive associate dean, education and clinical professor of geriatric medicine, UBC faculty of medicine UBC President and Vice-Chancellor Santa J. Ono and Vice President Health and Dr. Dermot Kelleher, dean, faculty of medicine and vice-president, health at UBC will also speak during the evening.
The musicians include two outstanding members of the Vienna Philharmonic – violinist Prof. Günter Seifert and violist-conductor Hans Peter Ochsenhofer, who will be joined by violinist-conductor Rémy Ballot and double bassist Dr. Manfred Hecking, who serves as a regular substitute in the orchestra.
For those in whose lives intertwine music and science, the experience of cross-connection will be familiar. For Dr. Penninger, the concert represents an opportunity to bring the famous sound of the Vienna Philharmonic to UBC and British Columbia, to a new audience. “That these musicians are coming here is a fantastic recognition and acknowledgement of the amazing work being done at UBC,” he says.
“Like poetry, music is a universal language that all of us immediately understand and can relate to. Science tells the most amazing stories. Both of them bring meaning and beauty to our world.”
“Sounds and Science” – Vienna Meets Vancouver is part of the President’s Concert Series | November 30, 2019 on campus at the Old Auditorium from 6:30 to 9:30 p.m.
To learn more about the Sounds and Science concert series hosted in cooperation with the Medical University of Vienna, visit www.soundsandscience.com.
I found more information regarding logistics,
Saturday, November 30, 2019 6:30 pm The Old Auditorium, 6344 Memorial Road, UBC Box office and Lobby: Opens at 5:30 pm (one hour prior to start of performance) Old Auditorium Concert Hall: Opens at 6:00 pm
The idea of combining music and medicine into the “Sounds & Science” – scientific concert series started in 2008, when the Austrian violinist Rainer Honeck played Bach’s Chaconne in d-minor directly before a keynote lecture, held by Nobel laureate Peter Doherty, at the Austrian Society of Allergology and Immunology’s yearly meeting in Vienna. The experience at that lecture was remarkable, truly a special moment. “Sounds & Science” was then taken a step further by bringing several concepts together: Anton Neumayr’s medical histories of composers, John Brockman’s idea of a “Third Culture” (very broadly speaking: combining humanities and science), and finally, our perception that science deserves a “Red Carpet” to walk on, in front of an audience. Attendees of the “Sounds & Science” series have also described that music opens the mind, and enables a better understanding of concepts in life and thereby science in general. On a typical concert/lecture, we start with a chamber music piece, continue with the pathobiography of the composer, go back to the music, and then introduce our main speaker, whose talk should be genuinely understandable to a broad, not necessarily scientifically trained audience. In the second half, we usually try to present a musical climax. One prerequisite that “Sounds & Science” stands for, is the outstanding quality of the principal musicians, and of the main speakers. Our previous concerts/lectures have so far covered several aspects of medicine like “Music & Cancer” (Debussy, Brahms, Schumann), “Music and Heart” (Bruckner, Mahler, Wagner), and “Music and Diabetes” (Bach, Ysaÿe, Puccini). For many individuals who have combined music and medicine or music and science inside of their own lives and biographies, the experience of a cross-connection between sounds and science is quite familiar. But there is also this “fun” aspect of sharing and participating, and at the “Sounds & Science” events, we usually try to ensure that the event location can easily be turned into a meeting place.
At a guess, Science and Sounds started informally in 2008 and became a formal series in 2014.
There is a video but it’s in German. It’s enjoyable viewing with beautiful music but unless you have German language skills you won’t get the humour. Also it runs for over 9 minutes (a little longer than most of videos you’ll find here on FrogHeart),