Category Archives: medicine

Human-on-a-chip predicts in vivo results based on in vitro model … for the first time

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

This paper is open access.

I happened to look at the paper and found good definitions of pharmacokinetics and pharmacodynamics. I know it’s not for everyone but if you’ve ever been curious about the difference (from the Introduction of On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships),

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.

Superhydrophobic nanoflowers

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.

A July 2, 2019 Texas A&M University news release (also on EurekAlert) by Jennifer Reiley, which originated the news item, expands on the theme,

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.

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

Superhydrophobic states of 2D nanomaterials controlled by atomic defects can modulate cell adhesion by Manish K. Jaiswal, Kanwar Abhay Singh, Giriraj Lokhande and Akhilesh K. Gaharwar. Chem. Commun., 2019, Advance Article DOI: 10.1039/C9CC00547A First published on 07 Jun 2019

This paper is open access.

Human-machine interfaces and ultra-small nanoprobes

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,

U-shaped nanowires can record electrical chatter inside a brain or heart cell without causing any damage. The devices are 100 times smaller than their biggest competitors, which kill a cell after recording. Courtesy: University of Surrey

A July 3, 2019 University of Surrey press release (also on EurekAlert), which originated the news item, provides more details about this UK/US/China collaboration,

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.

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

Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording by Yunlong Zhao, Siheng Sean You, Anqi Zhang, Jae-Hyun Lee, Jinlin Huang & Charles M. Lieber. Nature Nanotechnology (2019) DOI: https://doi.org/10.1038/s41565-019-0478-y Published 01 July 2019

The link I’ve provided leads to a paywall. However, I found a freely accessible version of the paper (this may not be the final published version) here.

The medical community and art/science: two events in Canada in November 2019

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.

I was able to find out more in a November 6, 2019 article at broadwayworld.com (Note: Some of this is repetitive),

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].

You can get more details and a link for ticket purchase here.

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

Sounds
Günter Seifert  VIOLIN
Rémy Ballot VIOLIN
Hans Peter Ochsenhofer VIOLA
Manfred Hecking DOUBLE BASS

Science
Josef Penninger GENETICS
Manfred Hecking INTERNAL MEDICINE
Troy Grennan INFECTIOUS DISEASE
Poul Sorensen PATHOLOGY & LABORATORY MEDICINE
Allison Eddy PEDIATRICS
Roger Wong GERIATRICS

Tickets are also available in person at UBC concert box-office locations:
– Old Auditorium
– Freddie Wood Theatre
– The Chan Centre for the Performing Art

General admission: $10.00
Free seating for UBC students
Purchase tickets for both President’s Concert Series events to make it a package, and save 10% on both performances

Transportation
Public and Bike Transportation
Please visit Translink for bike and transit information.
Parking
Suggested parking in the Rose Garden Parkade.

Buy Tickets

The Sounds and Science website has a feature abut the upcoming Vancouver concert and it offers a history dating from 2008,

MUSIC AND MEDICINE

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),

Enjoy!

Bacteria and graphene oxide as a basis for producing computers

A July 10, 2019 news item on ScienceDaily announces a more environmentally friendly way to produce graphene leading to more environmentally friendly devices such as computers,

In order to create new and more efficient computers, medical devices, and other advanced technologies, researchers are turning to nanomaterials: materials manipulated on the scale of atoms or molecules that exhibit unique properties.

Graphene — a flake of carbon as thin as a single later of atoms — is a revolutionary nanomaterial due to its ability to easily conduct electricity, as well as its extraordinary mechanical strength and flexibility. However, a major hurdle in adopting it for everyday applications is producing graphene at a large scale, while still retaining its amazing properties.

In a paper published in the journal ChemOpen, Anne S. Meyer, an associate professor of biology at the University of Rochester [New York state, US], and her colleagues at Delft University of Technology in the Netherlands, describe a way to overcome this barrier. The researchers outline their method to produce graphene materials using a novel technique: mixing oxidized graphite with bacteria. Their method is a more cost-efficient, time-saving, and environmentally friendly way of producing graphene materials versus those produced chemically, and could lead to the creation of innovative computer technologies and medical equipment.

A July 10, 2019 University of Rochester news release (also on EurekAlert), which originated the news item, provides details as to how this new technique for extracting graphene differs from the technique currently used,

Graphene is extracted from graphite, the material found in an ordinary pencil. At exactly one atom thick, graphene is the thinnest–yet strongest–two-dimensional material known to researchers. Scientists from the University of Manchester in the United Kingdom were awarded the 2010 Nobel Prize in Physics for their discovery of graphene; however, their method of using sticky tape to make graphene yielded only small amounts of the material.

“For real applications you need large amounts,” Meyer says. “Producing these bulk amounts is challenging and typically results in graphene that is thicker and less pure. This is where our work came in.”

In order to produce larger quantities of graphene materials, Meyer and her colleagues started with a vial of graphite. They exfoliated the graphite–shedding the layers of material–to produce graphene oxide (GO), which they then mixed with the bacteria Shewanella. They let the beaker of bacteria and precursor materials sit overnight, during which time the bacteria reduced the GO to a graphene material.

“Graphene oxide is easy to produce, but it is not very conductive due to all of the oxygen groups in it,” Meyer says. “The bacteria remove most of the oxygen groups, which turns it into a conductive material.”

While the bacterially-produced graphene material created in Meyer’s lab is conductive, it is also thinner and more stable than graphene produced chemically. It can additionally be stored for longer periods of time, making it well suited for a variety of applications, including field-effect transistor (FET) biosensors and conducting ink. FET biosensors are devices that detect biological molecules and could be used to perform, for example, real-time glucose monitoring for diabetics.

“When biological molecules bind to the device, they change the conductance of the surface, sending a signal that the molecule is present,” Meyer says. “To make a good FET biosensor you want a material that is highly conductive but can also be modified to bind to specific molecules.” Graphene oxide that has been reduced is an ideal material because it is lightweight and very conductive, but it typically retains a small number of oxygen groups that can be used to bind to the molecules of interest.

The bacterially produced graphene material could also be the basis for conductive inks, which could, in turn, be used to make faster and more efficient computer keyboards, circuit boards, or small wires such as those used to defrost car windshields. Using conductive inks is an “easier, more economical way to produce electrical circuits, compared to traditional techniques,” Meyer says. Conductive inks could also be used to produce electrical circuits on top of nontraditional materials like fabric or paper.

“Our bacterially produced graphene material will lead to far better suitability for product development,” Meyer says. “We were even able to develop a technique of ‘bacterial lithography’ to create graphene materials that were only conductive on one side, which can lead to the development of new, advanced nanocomposite materials.”

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

Creation of Conductive Graphene Materials by Bacterial Reduction Using Shewanella Oneidensis by Benjamin A. E. Lehner, Vera A. E. C. Janssen, Dr. Ewa M. Spiesz, Dominik Benz, Dr. Stan J. J. Brouns, Dr. Anne S. Meyer, Prof. Dr. Herre S. J. van der Zant. ChemistryOpen Volume 8, Issue 7 July 2019 Pages 888-895 DOI: https://doi.org/10.1002/open.201900186
First published: 04 July 2019

As you would expect given the journal’s title, this paper is open access.

Israeli startup (Nanomedic) and a ‘ray’ gun that shoots wound-healing skin

[downloaded from https://uploads.neatorama.com/images/posts/967/107/107967/Spray-on-Nanofiber-Skin-May-Improve-Burn-and-Wound-Care_0-x.jpg?v=10727]

Where I see a ‘ray’ gun, Rina Raphael, author of a July 6, 2019 article for Fast tCompany, sees a water pistol (Note: Links have been removed),

Imagine if bandaging looked a little more like, well, a water gun?

Israeli startup Nanomedic Technologies Ltd., a subsidiary of medical device company Nicast, has invented a new mechanical contraption to treat burns, wounds, and surgical injuries by mimicking human tissue. Shaped like a children’s toy, the lightweight SpinCare emits a proprietary nanofiber “second skin” that completely covers the area that needs to heal.

All one needs to do is aim, squeeze the two triggers, and fire off an electrospun polymer material that attaches to the skin.

The Nanomedic spray method avoids any need to come into direct contact with the wound. In that sense, it completely sidesteps painful routine bandage dressings. The transient skin then fully develops into a secure physical barrier with tough adherence. Once new skin is regenerated, usually between two to three weeks (depending on the individual’s heal time), the layer naturally peels off.

“You don’t replace it,” explains Nanomedic CEO Dr. Chen Barak. “You put it only once—on the day of application—and it remains there until it feels the new layer of skin healed.”

“It’s the same model as an espresso machine,” says Barak.

The SpinCare holds single-use ampoules containing Nanomedic’s polymer formulation. Once the capsule is firmly in place, one activates the device roughly eight inches towards the wound. Pressing the trigger activates the electron-spinning process, which sprays a web-like a layer of nano fibers directly on the wound.

The solution adjusts to the morphology of the wound, thereby creating a transient skin layer that imitates the skin structure’s human tissue. It’s a transparent, protective film that then allows the patient and doctor to monitor progress. Once the wound has healed and developed a new layer of skin, the SpinCare “bandage” falls off on its own.

The product is already being tested in hospitals. In the coming year, following FDA clearance, Nanomedic plans to expand to emergency rooms, ambulances, military use, and disaster relief response like fire truck companies. The global wound healing market is expected to hit $35 billion by 2025, according to a report by Transparency Market Research.

Nanomedic joins other researchers attempting to reimagine the wound healing process. Engineers at the University of Wisconsin-Madison, for example, created a new kind of protective bandage that sends a mild electrical stimulation, thereby “dramatically” reducing the time deep surgical wounds take to heal.

As for the the playful (yet functional) design, it resembles other medical tools utilizing the point-and-shoot feature. Researchers at the Technion-Israel Institute of Technology and Boston Children’s Hospital recently revealed a “hot-glue gun” that melds torn human tissues together. The medical glue is meant to replace painful and often scarring stitches and staples.

Down the line, Nanomedic plans to enter the in-home care market, where it believes it can better assist caretakers for treatment of chronic wounds, such as pressure ulcers. The chronic wounds segment is projected to hold the dominant share in the wound healing market due to aging populations.

But a bigger opportunity lies in the multiple uses the SpinCare can ultimately provide. It is, in essence, a platform technology that could benefit multiple categories, not just medical wound care. Currently, the SpinCare’s capsules do not contain any active ingredients.

Nanomedic is already researching how to add different additives, such as antibacterial compliments, collagen, silicone, cannabinoids—and, eventually, stem cells and cellular treatments.

Such advancements would propel the device to new markets, like plastic surgery, aesthetics, and dermatology. The latter, for example, spans “burns” caused by deep, cosmetic laser peels.

“Because it is a solution, we can combine additives inside,” explains Katz. “By that, we are transforming the transient skin into a drug delivery system and slow release system.”

Nanomedic is still at the premarket phase, [emphasis mine] having concluded one clinical trial related to the treatment of split graft donor site wounds and currently engaged in two ongoing burn studies. Barak anticipates FDA approval will take between nine to 12 months, during which the company will focus on building manufacturing lines and preparing for a European launch in early 2020.

According to the startup’s estimates, the product’s final price (not yet determined) will be far more affordable than traditional dressings. Nanomedic has raised $7 million in funding to date, including a grant by the EU’s Horizon 2020 SME Instrument program.

Barak believes Nanocare [sic] brings a highly cost-effective alternative to the healthcare system, but more than anything, she’s proud that SpinCare, above all else, mitigates patient pain and hassle. Some users, the company reports, are able to return to work and physical activity right away.

The Nanomedic website can be found here. The company has also produced a video featuring SpinCare,

There’s a bit more about the technology (I’m especially interested in the electrospinning) on Nanomedic’s Technology webpage,

Electrospinning technology allows the development of a wide range of products and devices, with tailored composition, geometry and morphology.

Almost any natural or synthetic polymer can be electrospun to create a nanofibrous mat. The intrinsic structure of the electrospun products, which mimics the natural extra cellular matrix (ECM), encourages quick and efficient tissue integration and minimizes medical complications.

Raphael’s article and the Nanomedic website offer more detail to what you can see in the excerpts provided here. If you have the time, I recommend checking out both.

Nanocellulose sensors: 3D printed and biocompatible

I do like to keep up with nanocellulose doings, especially when there’s some Canadian involvement, and an October 8, 2019 news item on Nanowerk alerted me to a newish application for the product,

Physiological parameters in our blood can be determined without painful punctures. Empa researchers are currently working with a Canadian team to develop flexible, biocompatible nanocellulose sensors that can be attached to the skin. The 3D-printed analytic chips made of renewable raw materials will even be biodegradable in future.

The idea of measuring parameters that are relevant for our health via the skin has already taken hold in medical diagnostics. Diabetics, for example, can painlessly determine their blood sugar level with a sensor instead of having to prick their fingers.

An October 8, 2019 Empa (Swiss Federal Laboratories for Materials Science and Technology) press release, which originated the news item, provides more detail,

A transparent foil made of wood

Nanocellulose is an inexpensive, renewable raw material, which can be obtained in form of crystals and fibers, for example from wood. However, the original appearance of a tree no longer has anything to do with the gelatinous substance, which can consist of cellulose nanocrystals and cellulose nanofibers. Other sources of the material are bacteria, algae or residues from agricultural production. Thus, nanocellulose is not only relatively easy and sustainable to obtain. Its mechanical properties also make the “super pudding” an interesting product. For instance, new composite materials based on nanocellulose can be developed that could be used as surface coatings, transparent packaging films or even to produce everyday objects like beverage bottles.

Researchers at Empa’s Cellulose & Wood Materials lab and Woo Soo Kim from the Simon Fraser University [SFU] in Burnaby, Canada, are also focusing on another feature of nanocellulose: biocompatibility. Since the material is obtained from natural resources, it is particularly suitable for biomedical research.

With the aim of producing biocompatible sensors that can measure important metabolic values, the researchers used nanocellulose as an “ink” in 3D printing processes. To make the sensors electrically conductive, the ink was mixed with silver nanowires. The researchers determined the exact ratio of nanocellulose and silver threads so that a three-dimensional network could form.

Just like spaghetti – only a wee bit smaller

It turned out that cellulose nanofibers are better suited than cellulose nanocrystals to produce a cross-linked matrix with the tiny silver wires. “Cellulose nanofibers are flexible similar to cooked spaghetti, but with a diameter of only about 20 nanometers and a length of just a few micrometers,” explains Empa researcher Gilberto Siqueira.

The team finally succeeded in developing sensors that measure medically relevant metabolic parameters such as the concentration of calcium, potassium and ammonium ions. The electrochemical skin sensor sends its results wirelessly to a computer for further data processing. The tiny biochemistry lab on the skin is only half a millimeter thin.

While the tiny biochemistry lab on the skin – which is only half a millimeter thin – is capable of determining ion concentrations specifically and reliably, the researchers are already working on an updated version. “In the future, we want to replace the silver [nano] particles with another conductive material, for example on the basis of carbon compounds,” Siqueira explains. This would make the medical nanocellulose sensor not only biocompatible, but also completely biodegradable.

I like the images from Empa better than the ones from SFU,

Using a 3D printer, the nanocellulose “ink” is applied to a carrier plate. Silver particles provide the electrical conductivity of the material. Image: Empa
Empa researcher Gilberto Siqueira demonstrates the newly printed nanocellulose circuit. After a subsequent drying, the material can be further processed. Image: Empa

SFU produced a news release about this work back in February 2019. Again, I prefer what the Swiss have done because they’re explaining/communicating the science, as well as , communicating benefits. From a February 13, 2019 SFU news release (Note: Links have been removed),

Simon Fraser University and Swiss researchers are developing an eco-friendly, 3D printable solution for producing wireless Internet-of-Things (IoT) sensors that can be used and disposed of without contaminating the environment. Their research has been published as the cover story in the February issue of the journal Advanced Electronic Materials.

SFU professor Woo Soo Kim is leading the research team’s discovery, which uses a wood-derived cellulose material to replace the plastics and polymeric materials currently used in electronics.

Additionally, 3D printing can give flexibility to add or embed functions onto 3D shapes or textiles, creating greater functionality.

“Our eco-friendly, 3D-printed cellulose sensors can wirelessly transmit data during their life, and then can be disposed without concern of environmental contamination,” says Kim, a professor in the School of Mechatronic Systems Engineering. The SFU research is being carried out at PowerTech Labs in Surrey, which houses several state-of-the-art 3D printers used to advance the research.

“This development will help to advance green electronics. For example, the waste from printed circuit boards is a hazardous source of contamination to the environment. If we are able to change the plastics in PCB to cellulose composite materials, recycling of metal components on the board could be collected in a much easier way.”

Kim’s research program spans two international collaborative projects, including the latest focusing on the eco-friendly cellulose material-based chemical sensors with collaborators from the Swiss Federal Laboratories for Materials Science.

He is also collaborating with a team of South Korean researchers from the Daegu Gyeongbuk Institute of Science and Technology’s (DGIST)’s department of Robotics Engineering, and PROTEM Co Inc, a technology-based company, for the development of printable conductive ink materials.

In this second project, researchers have developed a new breakthrough in the embossing process technology, one that can freely imprint fine circuit patterns on flexible polymer substrate, a necessary component of electronic products.

Embossing technology is applied for the mass imprinting of precise patterns at a low unit cost. However, Kim says it can only imprint circuit patterns that are imprinted beforehand on the pattern stamp, and the entire, costly stamp must be changed to put in different patterns.

The team succeeded in developing a precise location control system that can imprint patterns directly resulting in a new process technology. The result will have widespread implications for use in semiconductor processes, wearable devices and the display industry.

This paper was made available online back in December 2018 and then published in print in February 2019. As to why there’d be such large gaps between the paper’s publication dates and the two institution’s news/press releases, it’s a mystery to me. In any event, here’s a link to and a citation for the paper,

3D Printed Disposable Wireless Ion Sensors with Biocompatible Cellulose Composites by Taeil Kim, Chao Bao, Michael Hausmann, Gilberto Siqueira, Tanja Zimmermann, Woo Soo Kim. Advanced Electronic Materials DOI: https://doi.org/10.1002/aelm.201970007 First published online December 19, 2018. First published in print: 08 February 2019 (Adv. Electron. Mater. 2/2109) Volume 5, Issue 2 February 2019 1970007

This paper is behind a paywall.

Gold nanoparticle loaded with CRISPR used to edit genes

CRISPR (clustered regularly interspaced short palindromic repeats) gene editing is usually paired with a virus (9, 12a, etc.) but this time scientists are using a gold nanoparticle. From a May 27, 2019 news item on Nanowerk (Note: Links have been removed),

Scientists at Fred Hutchinson Cancer Research Center took a step toward making gene therapy more practical by simplifying the way gene-editing instructions are delivered to cells. Using a gold nanoparticle instead of an inactivated virus, they safely delivered gene-editing tools in lab models of HIV and inherited blood disorders, as reported in Nature Materials (“Targeted homology-directed repair in blood stem and progenitor cells with CRISPR nanoformulations”).

A May 27, 2019 Fred Hutchinson Cancer Research Center news release (also on EurekAlert) by Jake Siegel, which originated the news item, expands on the theme, provides more detail,

It’s the first time that a gold nanoparticle loaded with CRISPR has been used to edit genes in a rare but powerful subset of blood stem cells, the source of all blood cells. The CRISPR-carrying gold nanoparticle led to successful gene editing in blood stem cells with no toxic effects.

“As gene therapies make their way through clinical trials and become available to patients, we need a more practical approach,” said senior author Dr. Jennifer Adair, an assistant member of the Clinical Research Division at Fred Hutch, adding that current methods of performing gene therapy are inaccessible to millions of people around the world. “I wanted to find something simpler, something that would passively deliver gene editing to blood stem cells.”

While CRISPR has made it faster and easier to precisely deliver genetic modifications to the genome, it still has challenges. Getting cells to accept CRISPR gene-editing tools involves a small electric shock that can damage and even kill the cells. And if precise gene edits are required, then additional molecules must be engineered to deliver them –adding cost and time.

Gold nanoparticles are a promising alternative because the surface of these tiny spheres (around 1 billionth the size of a grain of table salt) allows other molecules to easily stick to them and stay adhered.

“We engineered the gold nanoparticles to quickly cross the cell membrane, dodge cell organelles that seek to destroy them and go right to the cell nucleus to edit genes,” said Dr. Reza Shahbazi, a Fred Hutch postdoctoral researcher who has worked with gold nanoparticles for drug and gene delivery for seven years.

Shahbazi made the gold particles from laboratory-grade gold that is purified and comes as a liquid in a small lab bottle. He mixed the purified gold into a solution that causes the individual gold ions to form tiny particles, which the researchers then measured for size.

They found that a particular size – 19 nanometers wide – was the best for being big and sticky enough to add gene-editing materials to the surface of the particles, while still being small enough for cells to absorb them.

Packed onto the gold particles, the Fred Hutch team added these gene-editing components (diagram available [see below]):

A type of molecular guide called crRNA acts as a genetic GPS to show the CRISPR complex where in the genome to make the cut.

CRISPR nuclease protein, often called “genetic scissors,” makes the cut in the DNA. The CRISPR nuclease protein most often used is Cas9. But the Fred Hutch researchers also studied Cas12a (formerly called Cpf1) because Cas12a makes a staggered cut in DNA. The researchers hoped this would allow the cells to more efficiently repair the cut and while so doing embed the new genetic instructions into the cell. Another advantage of Cas12a over Cas9 is that it only requires one molecular guide, which is important because of space constraints on the nanoparticles. Cas9 requires two molecular guides.

Instructions for what genetic changes to make (“ssDNA”). The Fred Hutch team chose two inherited genetic changes that bestow protection from disease: CCR5, which protects against HIV, and gamma hemoglobin, which protects against blood disorders such as sickle cell disease and thalassemia.

A coating of a polyethylenimine swarms the surface of the particles to give them a more positive charge, which enables them to more readily be absorbed into cells. This is an improvement over another method of getting cells to take up gene editing tools, called electroporation, which involves lightly shocking the cells to get them to open and allow the genetic instructions to enter.

Then the researchers isolated blood stem cells with a protein marker on their surface called CD34. These CD34-positive cells contain the blood-making progenitor cells that give rise to the entire blood and immune system.

“These cells replenish blood in the body every day, making them a good candidate for one-time gene therapy because it will last a lifetime as the cells replace themselves,” Adair said.

Observing human blood stem cells in a lab dish, the researchers found that their fully loaded gold nanoparticles were taken up naturally by cells within six hours of being added and within 24 to 48 hours they could see gene editing happening. They observed that the Cas12a CRISPR protein partner was better at delivering very precise genetic edits to the cells than the more commonly used cas9 protein partner.

The gene-editing effect reached a peak eight weeks after the researchers injected the cells into mouse models; 22 weeks after injection the edited cells were still there. The Fred Hutch researchers also found edited cells in the bone marrow, spleen and thymus of the mouse models, a sign that the dividing blood cells in those organs could carry on the treatment without the mice having to be treated again.

“We believe we have a good candidate for two diseases — HIV and hemoglobinopathies — though we are also evaluating other disease targets where small genetic changes can have a big impact, as well as ways to make bigger genetic changes,” Adair said. “The next step is to increase how much gene editing happens in each cell, which is definitely doable. That will make it closer to being an effective therapy.”

In the study, the researchers report 10 to 20 percent of cells took on the gene edits, which is a promising start, but the researchers would like to aim for 50% or more of the cells being edited, which they believe will have a good chance of combatting these diseases.

###

Adair and Shahbazi are looking for commercial partners to develop the technology into therapies for people. They hope to begin clinical trials within a few years.

Here’s the diagram of a gold nanoparticle loaded with CRISPR,

Caption: Graphic of a fully loaded gold nanoparticle with CRISPR and other gene editing tools. Credit: Image courtesy of the Adair lab at Fred Hutch.

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

Targeted homology-directed repair in blood stem and progenitor cells with CRISPR nanoformulations by Reza Shahbazi, Gabriella Sghia-Hughes, Jack L. Reid, Sara Kubek, Kevin G. Haworth, Olivier Humbert, Hans-Peter Kiem & Jennifer E. Adair. Nature Materials (2019) DOI https://doi.org/10.1038/s41563-019-0385-5Published 27 May 2019

This paper is behind a paywall.

Skin-based vaccination delivery courtesy of nanotechnology

A May 28, 2019 news item on Nanowerk announced research targeting Langerham cells and the immune system (Note: A link has been removed),

Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam developed targeted nanoparticles that are taken up by certain immune cells of the human skin (ACS Central Science, “A specific, glycomimetic Langerin ligand for human Langerhans cell targeting”). These so-called Langerhans cells coordinate the immune response and alert the body when pathogens or tumors occur.

This new nanoparticle technology platform enables targeted drug delivery of vaccines or pharmaceuticals to Langerhans cells, triggering a controlled immune response to naturally eradicate the pathogen or tumor.

Internalized nanoparticles (red) in a Langerhans cell (green membrane marker). Specific targeting of these skin immune cells may lead to novel approaches for skin vaccination [weniger] © Langerhans Zellforschung Labor an der Medizinischen Universität Innsbruck Courtesy: Max Planck Institute

A May 28,2019 Max Planck Institute (MPI) press release, which originated the news item, provides further explanations,

The skin is a particularly attractive place for the application of many drugs that affect the immune system, as the appropriate target cells lie directly beneath the skin. These Langerhans cells are able to elicit an immune reaction in the entire body of the patient after local application of an active substance.

Langerhans Cells – Experts of pathogen defense

To develop a targeted drug delivery system, which guides drugs directly to Langerhans cells, one can make use of their natural function: as professional, antigen-presenting cells they detect pathogens, internalize them and present components of these pathogens to effector cells of the immune system (T cells). For detection and uptake, Langerhans cells use receptors on their surface that search the environment for microbes. They especially recognize pathogens by the unique coating of sugar structures on their surface. Langerin, a protein of the C-type lectins family, is such a receptor on Langerhans cells that can detect viruses and bacteria. The specific expression of Langerin on Langerhans cells allows a targeted drug delivery encapsulated in nanoparticleswhile minimizing the side effects.

The research team of Dr. Christoph Rademacher at the Max Planck Institute of Colloids and Interfaces has now been able to exploit the knowledge of the underlying detection mechanisms with atomic resolution: “Based on our insight how immune cells recognize sugars, we developed a synthetic, sugar-like substance that enables nanoparticles to specifically bind to Langerhans cells”, says Dr. Christoph Rademacher. In collaboration with a scientific team from the Laboratory for Langerhans Cell Research of the Medical University of Innsbruck, nanoparticles have been developed that can be incorporated into Langerhans cells of the human skin through this interaction. The researchers thus lay the foundation for further developments, for example to deliver vaccines directly through the skin to the immune cells. “Imagine avoiding needles for vaccination in the future or directly activating the body’s immune system against infections and maybe even cancer”, adds Dr. Christoph Rademacher. Langerhans cells are responsible for activating the immune system systemically. Based on these findings, it may be possible in the future to develop novel vaccines against infections or immunotherapies for the treatment of cancer or autoimmune diseases.

The starting points for this work were the pioneering contributions from Ralph M. Steinman (Nobel Prize 2011) and other scientists who showed the potential of dendritic cells. Langerhans cells are one subset of these cells and are able to trigger an immune response. These findings were subsequently refined for use in cancer therapy. It has been shown that an immune response can be achieved via artificially introduced antigens. Later work confirmed these findings and also demonstrated that human Langerhans cells are also able to activate the immune system, which is particularly interesting for skin vaccination. Targeted delivery of immunomodulators to Langerhans cells would thus be desirable. However, this is often hindered or even prevented by the complex environment of the skin, especially by competing phagocytes in this tissue, such as macrophages. Consequently, pharmaceuticals not taken up by the Langerhans cells, but internalized into bystander cells may lead to unwanted side effects.

Recognition through synthetic sugars

Based on insights on the interaction between Langerin and its natural sugar ligands Christoph Rademacher and his team developed a synthetic ligand, which binds specifically to the receptor on Langerhans cells. For this purpose, synthetic sugars were produced in the laboratory and their interactions with the receptor were examined by nuclear magnetic resonance spectroscopy. With this method the researchers were able to determine which atoms of the ligand interact with which parts of the receptor. By using this structure-based approach they found out that a compound can be anchored and tested on these nanoparticles. These particles are liposomes, which have been used for many years in the clinic in the absence of such targeting ligands as a carrier for various drugs. The difference with existing systems is that the sugar-like ligand now allows specific binding to Langerhans cells. The investigations on these immune cells were carried out in collaboration with the research group of Assoz. Prof. Patrizia Stoitzner at the Langerhans Cell Research Laboratory of the Medical University of Innsbruck. Together they could show that the specific uptake of liposomes is possible even in the complex environment of human skin. The scientists used different methods such as flow cytometry and confocal microscopy for their findings.

These liposomal particles may now provide a common platform for researchers at the MPI of Colloids and Interfaces to work on the development of novel vaccines in the future.

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

A Specific, Glycomimetic Langerin Ligand for Human Langerhans Cell Targeting by Eike-Christian Wamhoff, Jessica Schulze, Lydia Bellmann, Mareike Rentzsch, Gunnar Bachem, Felix F. Fuchsberger, Juliane Rademacher, Martin Hermann, Barbara Del Frari, Rob van Dalen, David Hartmann, Nina M. van Sorge, Oliver Seitz, Patrizia Stoitzner, Christoph Rademacher. ACS Cent. Sci.201955808-820 DOI: https://doi.org/10.1021/acscentsci.9b00093 Publication Date: May 10, 2019 Copyright © 2019 American Chemical Society

This paper appears to be open access.

Art/science and a paintable diagnostic test for cancer

One of Joseph Cohen’s painting incorporating carbon nanotubes photographed in normal light. Photo courtesy of Joseph Cohen. [downloaded from https://news.artnet.com/art-world/carbon-nanotube-cancer-paint-1638340?utm_content=from_&utm_source=Sailthru&utm_medium=email&utm_campaign=Global%20September%202%20PM&utm_term=artnet%20News%20Daily%20Newsletter%20USE%20%2830%20Day%20Engaged%20Only%29]

The artist credited with the work seen in the above, Joseph Cohen, has done something remarkable with carbon nanotubes (CNTs). Something even more remarkable than the painting as Sarah Cascone recounts in her August 30, 2019 article for artnet.com (Note: A link has been removed),

Not every artist can say that his or her work is helping in the fight against cancer. But over the past several years, Joseph Cohen has done just that, working to develop a new, high-tech paint that can be used not only on canvas, but also to detect cancers and medical conditions such as hypertension and diabetes.

Sloan Kettering Institute scientist Daniel Heller first suggested that Cohen come work at his lab after seeing the artist’s work, which is often made with pigments that incorporate diamond dust and gold, at the DeBuck Gallery in New York.

“We initially thought that in working with an artist, we would make art to shed a little light on our science for the public,” Heller told the Memorial Sloan Kettering blog. “But the collaboration actually taught us something that could help us shine a light on cancer.”

For Cohen, the project was initially intended to develop a new way of art-making. In Heller’s lab, he worked with carbon nanotubes, which Heller was already employing in cancer research, for their optical properties. “They fluoresce in the infrared spectrum,” Cohen says. “That gives artists the opportunity to create paintings in a new spectrum, with a whole new palette of colors.”

Because human eyesight is limited, we can’t actually see infrared fluorescence. But using a special short-wave infrared camera, Cohen is able to document otherwise invisible effects, revealing the carbon nanotube paint’s hidden colors.

“What you’re perceiving as a static painting is actually in motion,” Cohen says. “I’m creating paintings that exist outside of the visible experience.”

Art Supplies—and a Diagnostic Tool

That same imaging technique can be used by doctors looking for microalbuminuria, a condition that causes the kidneys to leak trace amounts of albumin into urine, which is an early sign of of several cancers, diabetes, and high blood pressure.

Cohen helped co-author a paper published this month in Nature Communications about using the nanosensor paint in litmus paper tests with patient urine samples. The study found that the paint, when viewed through infrared light, was able to reveal the presence of albumin based on changes in the paint’s fluorescence after being exposed to the urine sample.

“It’s easy to detect albumen with a dipstick if there’s a lot of levels in the urine, but that would be like looking at stage four cancer,” Cohen says. “This is early detection.”

What’s more, a nanosensor paint can be easily used around the world, even in poor areas that don’t have access to the best diagnostic technologies. Doctors may even be able to view the urine samples using an infrared imaging attachments on their smartphones.

One of Joseph Cohen’s painting incorporating carbon nanotubes shown in both the visible light (left) and in UV fluorescence (right). Photo courtesy of Joseph Cohen. [downloaded from https://news.artnet.com/art-world/carbon-nanotube-cancer-paint-1638340?utm_content=from_&utm_source=Sailthru&utm_medium=email&utm_campaign=Global%20September%202%20PM&utm_term=artnet%20News%20Daily%20Newsletter%20USE%20%2830%20Day%20Engaged%20Only%29]

Amazing, eh? If you have the time, do read Cascone’s article in its entirety and should your curiosity be insatiable, there’s also an August 22, 2019 posting by Jim Stallard on the Memorial Sloan Kettering Cancer Center blog,

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

Synthetic molecular recognition nanosensor paint for microalbuminuria by Januka Budhathoki-Uprety, Janki Shah, Joshua A. Korsen, Alysandria E. Wayne, Thomas V. Galassi, Joseph R. Cohen, Jackson D. Harvey, Prakrit V. Jena, Lakshmi V. Ramanathan, Edgar A. Jaimes & Daniel A. Heller. Nature Communicationsvolume 10, Article number: 3605 (2019) DOI: https://doi.org/10.1038/s41467-019-11583-1 Published: 09 August 2019

This paper is open access.

Joseph Cohen has graced this blog before in a May 3, 2019 posting titled, Where do I stand? a graphene artwork. It seems Cohen is very invested in using nanoscale carbon particles for his art.