M BIOSCI 0517-Cover-p01.indd - IOPscience

1 downloads 67 Views 4MB Size Report
23 Jun 2017 - The convergence of science and technol- ogy has been the catalyst for significant progress in tissue engin
ioppublishing.org/biosciences Annual review 2017

Taking research from the lab to the clinic Dynamic future for 4D bioprinting p12 Precision counts for ion-beam therapy p13 Magnetic nanoparticles help to detect cancer p15

M BIOSCI 0517-Cover-p01.indd 1

23/06/2017 10:41

APPLY YOUR EXPERTISE TO CANCER THE PIONEER AWARD FUNDS REVOLUTIONARY IDEAS FROM ANY DISCIPLINE PROCESS A unique anonymous application process ensures the best ideas are funded

1. SUBMIT YOUR IDEA

2. COMMITTEE SHORTLISTS

THREE DEADLINES EACH YEAR Find out more at cruk.org/pioneeraward

3. YOU PITCH

4. WE FUND UP TO £200,000

Biosciences: taking research from the lab to the clinic

Contents

ioppublishing .or g /biosciences

Taking research from the lab to the clinic Welcome

5

Q&A: Jos Malda

6

Jos Malda, president of the International Society for Biofabrication, stresses the importance of collaboration in the quest to create biological structures that might have the potential to replace human organs Jos Malda celebrates the power of collaboration p6

Q&A: Tami Freeman

7

Tami Freeman, editor of online news service medicalphysicsweb.org, unveils exciting plans to relaunch the site with new content and a new home in 2017

Biomaterials and bioengineering

9

A longer-lasting heart valve ● 3D bioprinter fabricates human skin ● Biomaterials benefit from plasma processing ● Microstimulation could restore lost touch ● Stem-cell spray offers gum repair ● 4D bioprinting: adding dynamic actuation ●

Cancer diagnosis and therapy

13

Ion-beam therapy becomes more precise ● Squeezing cells yields cancer clues ● Tomography sheds light on tumour progression ● Proton therapy: the benefits and challenges ●

Extending the lifetime of heart implants p9

Q&A: Simon Hattersley

15

Simon Hattersley, co-founder of Endomagnetics, explains how technology that exploits magnetic nanoparticles had been developed to detect cancer.

Analysis and diagnostics ● ●

More precise ion-beam therapy p13

Copyright © 2017 by IOP Publishing Ltd and individual contributors. All rights reserved

Towards the first full-body PET scanner Green light for photodynamic diagnosis Canine diagnosis put to the test ● Magnetic imaging captures beating heart

Biophysics ●

Editor Susan Curtis Contributing Editor Tami Freeman Production Editor Alison Gardiner Senior Marketing Executive Anastasia Ireland Advertisement Sales Chris Thomas Advertisement Production Mark Trimnell Diagram Artist Alison Tovey Art Director Andrew Giaquinto Associate Director Pernille Hammelsø

17 ●



Liquid breathing moves a step closer ● Molecular movements in biomembranes Modelling reveals bacteria behaviour ● Focus on network physiology

News from IOP Publishing ● ● ●

19

21

Biophysical Society partners on ebooks ● Peer review under the spotlight Discover more with Physics World ebooks ● Rewards for reviewers From acceptance to online in 24 hours

Adding value to IOP authors

23

How IOP Publishing can help you to promote and share your research

IOP journals in the biosciences Temple Circus, Temple Way, Bristol BS1 6HG, UK Tel +44 (0)117 929 7481 E-mail [email protected] Web ioppublishing.org

26

Find out more about all journals published by IOP Publishing in medical physics, biophysics and biomedical engineering

3 M BIOSCI 0517-Contents-p03.indd 3

23/06/2017 10:42

IOP Expanding Physics

TM

IOP Expanding Physics

IOP Expanding Physics

IOP Expanding Physics

IOP Expanding Physics

Physics of Cancer

A Short Course on Relativistic Heavy-Ion Collisions

Semiconductors

Renewables

Claudia Tanja Mierke

Bonds and bands

A review of sustainable energy supply options

David K Ferry

David Elliott

Asis Chaudhuri

IOP Expanding Physics

IOP Expanding Physics

IOP Expanding Physics

IOP Expanding Physics

Physics of the Atmosphere

Evolutionary Dynamics

Ahead of the Curve

Dynamical Properties in Nanostructured and Low-Dimensional Materials

Rodrigo Caballero

The mathematics of genes and traits

Hugo van den Berg

Hidden breakthroughs in the biosciences

Edited by Michael Levin Dany Adams VOLUME ONE

IOP Concise Physics

Michael G Cottam

TM

IOP Concise Physics A Morgan & Claypool Publication

IOP Concise Physics A Morgan & Claypool Publication

IOP Concise Physics A Morgan & Claypool Publication

IOP Concise Physics A Morgan & Claypool Publication

Capture and Relaxation in Semiconductor Quantum Dots

Defining and Measuring Nature

Skin Photoaging

The make of all things

An Introduction to Liquid Crystals through Experiments

R Ferreira Gérald Bastard

Jeffrey Huw Williams

˘epi˘c Mojca C

Rui Yin Qiquan Chen Michael R Hamblin

For more information about purchase options please contact [email protected] or to see the latest titles visit iopscience.org/books

internals ads.indd 23

23/06/2017 11:35

Biosciences: taking research from the lab to the clinic ioppublishing .or g /biosciences

Welcome Success in the biosciences has been driven by a strong focus on interdisciplinary research. This collaborative approach has yielded far-reaching discoveries and exciting new technologies, such as cell engineering, gene therapy and smart biomaterials, all of which offer enormous potential for delivering the treatments and even cures of tomorrow. And some of the most significant breakthroughs have been published in IOP Publishing’s portfolio of journals in the biosciences, as shown by the work highlighted in this special collection.

Cover image: Improved technologies for sequencing ribonucleic acid (RNA) are helping researchers to understand the causes of the disease. Photo courtesy of istockphoto.com.

The portfolio includes 11 journals, which together publish more than 3500 papers every year. Alongside the journals is an online news service, medicalphysicsweb.org, as well as an expanding series of ebooks that is supported by collaborations with society partners such as the Institute of Physics in Engineering and Medicine and the Biophysical Society. Taken together, our biosciences portfolio is dedicated to providing the community with essential content covering all areas of the field, ranging from fundamental research through to clinical applications. For 2017, we are pleased to introduce three major new initiatives in direct response to feedback from the community. The first recognizes the ongoing debate around alternative models of peer review, with a 12-month trial of double-blind peer review for authors of Biomedical Physics and Engineering Express (BPEX) who choose this option on submission. We have also launched a rapid publication service called Accepted Manuscripts, which allows the authors’ version of the manuscript to be made available and citable just 24 hours after acceptance. And you can find out on p7 how we are planning to relaunch medicalphysicsweb.org with an expanded remit that will encompass bioengineering and biophysics as well as medical physics. This special collection once again showcases what can only be a small selection of the most exciting research published across our biosciences titles this year. It includes short reports describing the 3D bioprinting of skin, and what could become a full-body PET scanner in the near future, among many other significant achievements. To find out more, you will find a full rundown of our journals on pp26–27. Finally, I would like to take this opportunity to thank all of our authors, referees, Editorial Board members and society partners for their ongoing contributions to our expanding publishing programme. We hope that you will enjoy this collection, and that we have the opportunity to work with you in 2017 and beyond.

Pernille Hammelsø Associate Director IOP Publishing [email protected]

5 M BIOSCI 0517-Welcome-p05.indd 1

23/06/2017 10:43

Biosciences: taking research from the lab to the clinic

Q&A: Jos Malda

ioppublishing .or g /biosciences

Biofabrication

Meeting of minds yields research success Jos Malda, president of the International Society for Biofabrication, stresses the importance of collaboration in the quest to create biological structures that might have the potential to replace human organs. You are now the president of the International Society for Biofabrication (ISBF). What are your key aims and objectives for the society?

Our starting point is that biofabrication is a multidisciplinary endeavour that needs to bring together expertise from many different fields, ranging from basic biology to engineering and even information science. The key aim of the Society is to bring all of these different disciplines together, and also to provide the crucial link between fundamental science, technological innovation, and the translation of new technologies into real-world applications. We know that each of us can’t make progress on our own; we need others to succeed. From the beginning, the Society was established as a collaboration between different geographic regions, and that remains an important part of our mission. Our annual conference rotates between Asia-Pacific, the Americas and Europe, and our board of directors includes representatives from each of these regions. This collaborative approach – between disciplines, between regions, and between pure and applied science – is essential for us to make meaningful progress.

How has the Society developed since it was founded in 2010?

The Society has enjoyed rapid growth in recent years, as can be shown by the number of attendees at our annual conference. In 2013, 40 people came to the conference in El Paso, Texas, while at last autumn’s event in Winston-Salem, North Carolina, that number had increased to almost 400. We are hoping that even more will attend the 2017 conference, which will be held in Beijing in October.

What do you think have been the most exciting advances in recent years?

The convergence of science and technology has been the catalyst for significant progress in tissue engineering and regenerative medicine over the last few years. From a biological perspective, we can now grow stem cells that produce specific functions, and at the same time we are apply-

sarily behave like the original organ. The cells need to interact and work together to provide the required function, and this becomes more difficult to achieve as the organ becomes larger. But one of the biggest challenges will be to translate this science and technology from the lab bench to the clinic. Much more needs to be done to understand how these fabricated structures might respond when implanted inside the body, and that will be crucial to gain regulatory approval for these techniques. Jos Malda President of the ISBF.

ing fabrication technologies, such as 3D printing, to create structures from living cells. We are now able to position cells with high precision in 3D space and, as we gain more control over that cell placement, it should be possible to improve the biological response of the artificial tissue. One significant outcome from this work would be to refine and even reduce our use of animal experimentation. We are also producing larger and more complex structures, which in time could potentially enable us to create entire organs that could be implanted into human patients. However, such implants would most likely not completely mimic a human organ, but they could be capable of reproducing the desired biological function.

What do you see as the biggest challenges and opportunities within the field?

One key challenge for researchers in this field is to ensure that the cells stay alive during the fabrication process, which makes it really important to provide an environment that supports living cells. As an example, we use bioinks for 3D printing, and for these we have two opposing requirements: on the one hand they must be fully biocompatible to keep the cells alive, and on the other they must be sturdy enough to support a 3D structure. It’s also important to realize that cells placed in a 3D structure – however lifelike the structure may be – won’t neces-

What are the challenges associated with working with scientists and engineers with expertise in such diverse disciplines?

It’s not really a challenge, but rather an opportunity. When a research group includes biologists, engineers and health professionals, it allows us to tackle a problem from many different perspectives. It is the best way to achieve real progress. At the same time, younger scientists now have the opportunity to participate in master’s programmes focused on the field of biofabrication. At my own institution, Utrecht University in the Netherlands, we have developed a programme in collaboration with the University of Würzburg in Germany and two universities in Australia, and one thing we do is to ensure that these young scientists can speak the language of the different disciplines. They also divide their time between Europe and Australia, exposing them to different environments and different approaches. It’s no longer enough to cover one subject or to stay in one location, and we believe that such broader exposure will help them in their future career.

How does a journal like Biofabrication support the research community?

In many ways Biofabrication has been a pioneering journal for us, largely because it is dedicated to this particular field. It provides an important mechanism for our community to disseminate the latest research results and, with an Impact Factor of 5.240, we can be confident of the quality of the work reported in the journal.

6 M BIOSCI 0517-Malda Q&A-p06.indd 9

23/06/2017 10:45

Biosciences: taking research from the lab to the clinic

Q&A: Tami Freeman

ioppublishing .or g /biosciences

medicalphysicsweb.org

Science news enters brave new world Tami Freeman, editor of online news service medicalphysicsweb.org, unveils exciting plans to relaunch the site with more content and a new home in 2017. medicalphysicsweb.org (MPW) has been providing news and information to researchers and practitioners since 2006. What is the secret of its success?

MPW offers readers an insight into the latest scientific breakthroughs within the broad field of medical physics, with a key focus on cancer diagnosis and therapy. It complements the primary research literature, which is mainly focused on enabling expert-to-expert communication, by taking a journalistic approach to report on the most significant new research in a clear, accessible way. This makes MPW ideal for anyone who wants a big-picture view of the latest developments in fields other than their own.

Who are the main readers for MPW?

MPW is aimed primarily at professional medical physicists, and our stats show that they come from all over the world. Some of our readers are based in academia, while others work in hospitals – as medical physicists, radiation oncologists or clinicians – as well as companies developing state-of-the-art medical technology. What unites them is that they are all exploiting or developing physics-based technologies to help detect and treat cancer, and they are all keen to understand the emerging tools and techniques that could ultimately improve outcomes for patients.

Given the success of MPW, why are you planning to change it?

There are several reasons. At the most basic, MPW now looks very dated and badly needs a makeover to bring it into the 21st century. The underlying technology also has its roots firmly in the 1990s, which makes it difficult to update the site and to respond to the changing needs of our readers. But as part of the relaunch project we have also taken the opportunity to re-evaluate the remit of the site and the content we provide through it. One key outcome is that we want to provide more dedicated coverage of related subjects in the biosciences, in particular biophysics and bioengineering, since these multidisciplinary fields have become increasingly important

Tami Freeman Editor of medicalphysicsweb.org.

“We want to provide more dedicated coverage of related subjects in the biosciences, in particular biophysics and bioengineering.” for us to understand the causes of disease and to find more effective ways to treat a variety of medical conditions. Another big change is that we will be integrating MPW and our expanded coverage of the biosciences into a revamped version of physicsworld.com, the awardwinning news service for the scientific community.

Why have you taken that decision?

When we launched MPW 11 years ago, there was very little overlap between disciplines, and so it made sense to have a separate site dedicated to covering the latest advances in medical physics (plus it’s worth noting that we also currently have specialist news services in the areas of nanotechnology and environmental science). As biomedical science has become more multidisciplinary – with biologists and clinicians working alongside chemists,

materials scientists and physicists – those distinct disciplines are becoming blurred, and we’ve had clear feedback from readers across all of our sites that they want to keep up to date with other subject areas that may be relevant to their work. One clear example of this change is in nanomedicine, where functionalized nanoparticles are being developed to deliver drugs into targeted locations within the body. The underlying techniques have emerged from the nanoscience community, but such targeted drug delivery will only be effective for medical applications if we can understand the chemical and physics processes at play inside the human body. Our aim in bringing together our coverage of medical physics with biosciences and bioengineering – and indeed with nanotechnolog y, materials science, photonics and other key disciplines in the physical and natural sciences – is to help readers to explore the connections between different subjects. At the same time, we will continue to provide the same coverage of medical physics within a dedicated area of the new Physics World site.

So what will happen to MPW?

MPW will become a specialist topic area within the Physics World site, which is being relaunched in Q3 2017 with a broad remit to cover all areas of the physical and natural sciences. The new Physics World site will also have a specialist topic area for biophysics and bioengineering. I will remain editor of the Medical Physics topic area – which will have its own homepage and weekly news alert – and my key task will be to continue to provide the very best coverage of new research across the key subdisclipines of radiotherapy, proton therapy, diagnostic imaging and nuclear medicine. But readers will benefit from a cleaner and more intuitive design, plus the opportunity to explore other content from across the Physics World portfolio.

How do you plan to expand your coverage of biophysics and bioengineering?

Over the last year or so we have made a concerted effort to boost our coverage of new research in these fields, even within

7 M BIOSCI 0517-Freeman Q&A-p09.indd 7

23/06/2017 10:45

Biosciences: taking research from the lab to the clinic

Q&A: Tami Freeman

ioppublishing .or g /biosciences

the confines of the current MPW. But we are also reaching out to the scientific community to help us develop our editorial programme in biophysics and bioengineering. As part of this initiative, we are really keen to offer a small number of PhD students the chance to boost their science communication skills by working with our professional science journalists to write research news stories for the site. They will get the chance to have their work read by scientists all over the world – and at the same time will improve their ability to communicate the significance of their own research to a broader community.

PhD students already have a busy schedule, and need to be committed to their research. How will they find time for this, and how will it help them?

We’re aware that PhD students have many demands on their time, so our idea is to build a network of 20 –25 student contributors, with each one writing one article per month. Their work will also be reviewed by other contributors and our professional journalists, providing ongoing feedback that will help each student to refine their science-writing skills. This should help anyone who is intent on a long-term career in aca-

demic research or industrial R&D, and should also enable contributors to gain a broader and deeper view of their own research field.

What support will you provide to the student contributors?

All contributors will be invited to an initial training session with me and other members of IOP Publishing’s awardw i n n i ng scienc e jou r na l ism tea m. Through the new site we will also ensure that all contributors (and their institutions) will receive full credit for their work, including an official “job title” plus author biogs and links to relevant research groups. In addition, each student will receive a welcome pack that will include free digital access to Physics World – the membership magazine of the Institute of Physics – and our complete portfolio of scientific ebooks, and more than 70 research journals.

How can students get involved with this initiative?

A nyone interested can just send an e-mail to me at [email protected]. I will send them some more detailed information about the project, and how they can get involved.

EBOOK PARTNERSHIP DELIVERS FIRST TITLE IN MEDICAL PHYSICS The first titles in a joint ebook series from the Institute of Physics and Engineering and Medicine (IPEM) and IOP Publishing are now being published on the IOPscience platform. Leading the way is Design and Shielding of Radiotherapy Treatment Facilities, edited by Patrick W Horton and David J Eaton, which provides a single point of reference for anyone involved in shielding design and radiation protection for radiotherapy facilities. The book brings together expertise on all treatment modalities, including megavoltage and kilovoltage photons, brachytherapy and high-energy particles, as well as conventional and Monte Carlo shielding calculations. It provides a comprehensive reference for qualified experts and radiation shielding designers, and is also useful for administrators, planners, architects, constructors and others involved in the design of radiotherapy facilities. Further titles in the series will be released during the rest of the year and into 2018.

Developing a label-free IVD? IMT’s precision glass solution delivers micron-level control at production scale manufacturing.

What’s in a Micron?

● Increased signal to noise ● Higher throughput ● Faster data acquisition

Manage your microns.

P R E C I S I O N

Learn more at IMTAG.ch

O N

G L A S S

IMT Masken und Teilungen AG CH-8606 Greifensee (Zürich) Switzerland Phone: +41 44 943 19 00 Fax: +41 44 943 19 01 [email protected] www.imtag.ch

8 M BIOSCI 0517-Freeman Q&A-p09.indd 8

23/06/2017 10:45

Biosciences: taking research from the lab to the clinic ioppublishing .or g /biosciences

Biomaterials and bioengineering

A longer-lasting heart valve Diseased heart valves can sometimes be replaced with biological substitutes from donors, but clinicians must usually rely on bioprosthetic valves based on tissues taken from animals. Researchers at the University of Padua have now shown that a new decellularization technique can prevent the factors that cause these replacement heart valves to deteriorate in the body, and even to be rejected after initial implantation. Bioprosthetic heart valves based on animal tissue, such as bovine pericardium, typically show structural deterioration after 10–15 years. The problem is thought to lie with the use of crosslinking agents such as glutaraldehyde (GA) in the treatment of animal pericardium before use, making it imperative to develop GA-free biological materials. The Italian research team has tested whether a new decellularization method called TRITDOC could solve the problem. Reporting their results in Biomedical Materials, they find that TRITDOC can eliminate the alpha-Gal xenoantigen, which is the main factor responsible for hyperacute rejection after transplantation. “The TRITDOC procedure does not affect the biological, mechanical and functional characteristics of the treated tissue,” explains first author Paola Aguiari. “It ensures cyto/ immunological properties superior or comparable to those of pericardial

Healing the heart A new biomaterial could extend the lifetime of bioprosthetic heart valves.

Biofabrication

The printed bilayered skin replicates the natural structure of skin. It has an external protective layer – the epidermis with its stratum corneum – and then a thicker, deeper layer called the dermis. This second layer consists of fibroblasts that produce collagen, the protein that gives skin its elasticity and mechanical strength. The researchers, who reported their results in Biofabrication, printed the bilayered skin using bioinks containing human plasma, as well as primary human fibroblasts and keratinocytes obtained from

3D bioprinter fabricates human skin A prototype 3D bioprinter that can create totally functional human skin has been developed by a Spanish research team. The skin is intended for transplant into patients with skin burns or wounds, and it can also be used for research and testing of cosmetic, chemical and pharmaceutical products.

zation, based on tests with human macrophage cells. Comparing TBP with two commercial bioprostheses, as well as GA-treated TBP, they found that cell adhesion 72 hours after seeding was significantly higher than on the other substrates. The number of adhered cells on TBP did not change from 24 to 72 h, while it significantly decreased on TBP-GA patches. All samples showed a significant increase in cytotoxity over time, as measured by the presence of LDH, an enzyme leaked from damaged cells. As a response, the macrophage cells seeded onto the pericardial samples released pro-inflammatory and anti-inflammatory cytokines, and after 72 h, TBP displayed a significantly higher anti/pro ratio than TBP-GA. This reduced activation of the complement system – a key event in the immune response to biomaterial implantation – suggests that TBP could provide a promising candidate material for production of prosthetic heart valves. “The aim of this study was to evaluate the compatibility of TBP with the immune system, and its potential to provide a suitable scaffold for cell adhesion/infiltration and proliferation without any cytotoxic effect,” said Aguiari. “The natural extension is aimed at testing the in vivo performances of the cellular scaffold. Currently, the biomaterial is employed in the manufacture of transcatheter valves, whose hydrodynamic behaviour and long-term tendency to calcific degeneration must be assessed."

patches currently used for manufacturing FDA-approved bioprosthetic heart valves.” After applying the TRITDOC protocol to bovine pericardium patches, Aguiari and colleagues showed that all cellular components and nucleic debris had been removed from the TRITDOC-decellularized bovine pericardium (TBP), and that the overall structural integrity of the extracellular matrix had been maintained. The researchers next investigated the efficacy of TRITDOC in eliminating alphaGal. Native bovine pericardium contained 26 × 1010 alphaGal epitopes per 10 mg of tissue, while no reactive alphaGal epitope was detected in TBP. This contrasts with the GA treatment applied to commercial bioprostheses, which does not completely mask the presence of alphaGal. The researchers also confirmed that TBP provides an effective scaffold for cell adhesion and coloni- Biomed. Mater. 11 015021

skin biopsies. Their technique generated 100 cm 2 of functional human skin in less than 35 minutes, which includes the 30 minutes required for fibrin gelation. Analysing the structure and function of the printed skin showed that it was similar to human skin and was indistinguishable from handmade bilayered dermo-epidermal equivalents. The development is currently being approved by European regulatory agencies to ensure that the skin is adequate for use on patients. Biofabrication 9 015006

9 M BIOSCI 0517-Biomaterials-p09-11.indd 11

23/06/2017 10:46

Biosciences: taking research from the lab to the clinic

Biomaterials and bioengineering

ioppublishing .or g /biosciences

Journal of Physics D: Applied Physics

Journal of Neural Engineering

Biomaterials benefit from plasma processing

Microstimulation could restore lost touch

Plasmas have long been used in the semiconductor industry to clean, etch and coat the materials used to fabricate computer chips, and now the same techniques are being put to work to engineer more effective biomaterials. “There are just so many things that you can do with plasma and biomaterials,” says Uroš Cvelbar of the surface engineering team at the Jožef Stefan Institute in Ljubljana, Slovenia. “We can deposit films, modify existing surfaces and add functionality – it’s a versatile technology.” To highlight some of the latest research in the field, Cvelbar has teamed up with Cristina Canal of the Technical University of Catalonia in Barcelona, Spain, and Masaru Hori of the University of Nagoya in Japan to guest edit a special issue on plasma-inspired biomaterials for Journal of Physics D: Applied Physics. Articles published in the issue show how plasmas at low temperatures can be used to create functional biomaterials and biocompatible surfaces that promote cell and tissue growth inside the body. Novel developments for diagnostics and sensing are also presented in the collection. “The issue covers all aspects of research that connect plasma and biomaterials,” says Cvelbar. “This includes plasma preparation of biomaterials for different applications (including soft tissues and hard tissues such as bone), plus drug delivery applications and antibacterial coatings. It also focuses on biological interactions of the novel plasmaprepared surfaces with bacteria, cells and tissues.”

SOME ARTICLES IN THIS ISSUE Non-thermal plasma technology for the development of antimicrobial surfaces: a review Anton Nikiforov et al J. Phys. D: Appl. Phys.49 204002 Novel biomaterials: plasma-enabled nanostructures and functions Igor Levchenko et al J. Phys. D: Appl. Phys.49 273001

Lost sensations, such as touch, could one day be restored using direct electrical stimulation of sensory neural pathways. Microstimulation from a single electrode has been shown to evoke sensations that are both place- and modality-specific, but so far those sensations have not felt “natural”. To induce a more realistic response, researchers from the Polytechnic Institute of NYU, SUNY Downstate and the University of Florida have developed a method that exploits multi-channel stimulation to deliver biomimetic spatiotemporal patterns to the somatosensory cortex. Their ultimate goal is to restore movement in patients who can no longer feel the sensation of touch. “Natural levels of proficiency in making dexterous movements require somatosensory feedback,” explains first author John Choi. “Algorithms for encoding touch stimuli artificially through electrode arrays have not yet been designed explicitly to evoke natural responses, and this is what we wanted to accomplish in our study.” Choi and colleagues developed their scheme using two microelectrode arrays implanted in the brains anaesthetized rats: one array in the forelimb to deliver microstimulation to the thalamus (the part of the brain that deals with sensory information); and the other in the primary somatosensory cortex to measure neural activity during stimulation. First, the researchers recorded template responses to physically touching a rat’s forepaw with varying pressure, duration and location. Next, they delivered single-pulse probing microstimulation, and used the neural responses to train a linear state-space model of the cortical response. The team then optimized a set of input pulse patterns to reproduce the naturally occurring responses to each touch type, and assessed the animals’ responses to natural touch and microstimulation. “The responses that our procedure 2016 JOURNAL IMPACT FACTOR

5.240

Touch test Stronger touches are reproduced more accurately than lighter ones.

Biofabrication iopscience.org/bf

generated for different touch locations and temporal patterns were very similar to the natural responses,” said Choi. “The responses also contained the same amount of information about touch parameters [pressure and location], with the same latency of information transfer.” Across all conditions and rats, the correlation coefficient between natural and virtual responses was 0.78 ± 0.05, increasing to 0.90 ± 0.03 for time periods within 100 ms of touch onset. Touching different digits on the rats’ paws activated overlapping but clearly distinct zones in the recording electrode array. Stronger touches were reproduced more accurately, and shorterduration touch patterns had higher accuracy than longer patterns. The researchers are now applying for funds to test the technique in humans. “One of the difficulties in working with animals is determining exactly how something feels to them, and therefore, we might not be able to answer the question of realism until we translate this work into humans,” Choi told medicalphysicsweb. One obstacle in translating this scheme to clinical application is that the method requires template responses to natural touch, which would not be available for patients with somatosensor y prostheses. Instead, the researchers envision that a microstimulation encoder could be initially optimized using templates generalized from another hemisphere, subject or from a nonhuman primate study, with simpler fine-tuning used to personalize the encoder for the patient. J. Neural Eng. 13 056007 Biofabrication™ focuses on cutting-edge research on the use of cells, proteins, biological materials and biomaterials as building blocks to manufacture biological systems and therapeutic products.

10 M BIOSCI 0517-Biomaterials-p09-11.indd 9

23/06/2017 10:51

Biosciences: taking research from the lab to the clinic

Biomaterials and bioengineering

ioppublishing .or g /biosciences

Biomedical Physics & Engineering Express

Stem-cell spray offers gum repair Left untreated, gum disease can develop into periodontitis, a condition that progressively destroys bone and the soft tissue around the teeth. The result can be tooth loss, and in the worst cases, patients may need surgery, including expensive boneand soft-tissue grafts. In situ tissue engineering, where stem and differentiated cells are applied to the damaged area, has the potential to improve treatment, and researchers in the US are developing a spray that could eventually deliver such cells directly into the oral cavity. In their latest work, reported in Biomedical Physics & Engineering Express, Wojtek Tutak and Gili Kaufman from the American Dental Association’s Dr Anthony Volpe Research Center and colleagues have shown that their device can be used to spray viable, multipotent cells.

The gas brush or g-brush has a coaxial geometry, where the culture medium containing the cells is delivered through a needle by a syringe pump. Carbon dioxide is pumped through an outer annulus that, upon ex iting a nozzle, mixes with the liquid. The resulting shear stresses break the liquid into droplets. This approach differs from existing clinical techniques that deliver the cells in a water-based gel. “Gels physically compress cells, restrict gas diffusion and provide a biochemical environment that is different from the environment in the patient’s wound,” says Tutak. “Ultimately, all these factors may slow down tissue regeneration.” Instead, the gas brush technique offers the potential to simultaneously spray several cell types that are needed to repair periodontal tissues.

Tooth spray Mouse cells sprayed onto a tooth have been shown to be viable three days later.

The researchers sprayed multipotent human bone marrow stromal cells (hBMSC) and mouse gingival fibroblasts (ESK-1) in separate, 0.25 ml “shots”. After culturing for 21 days, the viability of cells – as quantified with parameters such as DNA concentration – revealed no significant difference between g-brushing and pipetting, a technique commonly used to place cells on scaffolds and devices before implantation. The hBMSCs remained multipotent upon spraying, while the g-brush delivered cells more evenly than the pipette – which should boost the interactions between the cells and scaffold. ESK-1 cells were also sprayed onto the enamel and cementum coatings of a single tooth, and microscope images showed viable cells on the tooth three days after spraying. “We are very excited about the potential of this technique in clinical use,” says Kaufman, adding that more research is needed before animal studies can begin. Biomed. Phys. Eng. Express 2 035007

Non-Destructive Read (NDR) v v v



DaVinci-2K Low Noise CMOS Camera

High speed, continuous readout Post-hoc hoc integration time

NDR (1000 fps)

SNR

Event-based based imaging

v

True overlapped exposure

v

True 14 bit A/D with no A/D stitching

v

On-chip chip binning for deep well & higher speed, flexible configurations

Ø

Single Molecule Tracking

Ø

Super Resolution Microscopy

Ø

Applications with Low Light & Fast Changes Changes

SciMeasure Analytical Systems. Inc.

Conventional CDS (1000 fps) 2048x2048 at 200 fps ~1.1 billion pixel / sec

www.scimeasure.com Image courtesy of Dr. Cadby, Sheffield Univ. UK



M BIOSCI 0517-Biomaterials-p09-11.indd 10

11 23/06/2017 10:51

Biosciences: taking research from the lab to the clinic

Biomaterials and bioengineering

ioppublishing .or g /biosciences

Biofabrication

4D bioprinting: adding dynamic actuation A topical review in Biofabrication examines the potential of 4D bioprinting for creating biostructures with controllable motion, as Tami Freeman reports. Three-dimensional (3D) bioprinting is an enabling technology that allows high-precision fabrication of biological structures. But many biological systems perform unique functions in response to intrinsic or external stimuli, which means that static structures obtained from conventional 3D bioprinting may be unable to elicit realistic biological responses. What's needed is a fourth dimension: time. “Four-dimensional (4D) bioprinting has been proposed in recent years to emulate the dynamic processes seen in biological tissues,” explains Ali Khademhosseini from Harvard Medical School’s Biomaterials Innovation Research Center. “This is an exciting field with huge potential for development.” Writing in the journal Biofabrication, Khademhosseini and colleagues examine the potential of various stimuli-responsive materials as bioinks for 4D printing. They also discuss the current status of 3D printing, and look at future directions for 4D bioprinting platforms. “This is a key point in time where researchers are starting to move their attention to 4D bioprinting,” Khademhosseini told medicalphysicsweb. “We wanted to provide a thorough overview of the potential materials that can be possibly used in 4D bioprinting, and to spur collective efforts to push this field forward.”

Adding motion

Three main techniques have emerged for 3D bioprinting. Inkjet printing uses liquid bioink ejected in droplets to build a 3D volume, and typically offers high printing speed at low cost. Microextrusion printing, where bioinks are physically extruded by a dispensing system, benefits from the continuity of the extruded bioinks and can achieve high cell densities. Finally, laser-induced forward transfer printing works by focusing laser pulses on an absorbing layer, forcing

mable bioink, while materials can also be engineered to change size or shape in response to electric or magnetic stimulation. As an example, magnetic-responsive ferrogels have been exploited that control the release of drugs. But the highest precision can be achieved with light-sensitive materials that convert light into mechanical responses. Such materials have been widely applied in applications such as controlled drug delivery or cancer therapy, and could be combined with existing bioinks to enable 4D bioprinting.

A bright future

Bioprinting in the fourth dimension These “flowers” were fabricated through biomimetic 4D printing (Reprinted by permission from Macmillan Publishers Ltd: Nature Materials 15 413 © 2016).

Despite this large range of potential stimuli-responsive biomaterials, their translation into bioinks may not be straightforward. Existing materials must be engineered to ensure biocompatibility, ease of printing, and suitable stabilization mechanisms. It’s also important that embedded cells can survive the stimuli, and that the shape-changing capacity is not diminished by inclusion of cells. Another challenge lies in ensuring that 4D bioprinted constructs have robust shape-changing capabilities. Previous studies have shown the mechanical properties of printed objects to degrade severely after repeated transformations. As for the use of 4D bioprinting in clinical applications, this may still be decades away. “Right now the field is still in its infancy and concept stage,” Khademhosseini explained. “First, it requires a lengthy time to develop the variety of 4D bioprinting strategies, then we need to assess them in a thorough multi-phase clinical trial. This whole process involves not only the refinement and analysis of the biomaterials and encapsulated cells, but also ensuring that these smart structures actually behave and transform in the body in the ways that we design them to.”

a bioink droplet to deposit and form the desired pattern. To add shape transformation into printed structures, these 3D bioprinting platforms must be combined with stimuli-responsive biomaterials. One simple way to print structures that can actively transform is to deposit materials with differential properties (such as swelling) to achieve folding and unfolding. By using materials that expand to different degrees as joints between rigid segments, for example, the direction and angle of the joints can be controlled under suitable stimulus. Khademhosseini and colleagues describe the variety of transformation mechanisms that could potentially be integrated into 4D bioprinting. One approach is to use cells themselves as the active element. In this “cell origami” technique, the cell-traction force is harnessed to transform 3D microstructures into pre-defined shapes. By combining multiple cell types, complex cell-laden structures may be spontaneously formed in a post-printing procedure. Another option is to use stimuliresponsive materials as a program- Biofabrication 9 012001

12 M BIOSCI 0517-Feature-4D bioprinting-p12.indd 12

23/06/2017 10:52

Biosciences: taking research from the lab to the clinic ioppublishing .or g /biosciences

Cancer diagnosis and therapy

Ion-beam therapy becomes more precise Treating cancer patients with beams of carbon ions should be more effective than conventional radiotherapy, but the high precision offered by the technique has made it difficult for clinicians to control the radiation dose with sufficient accuracy. Now, researchers in Germany have reduced the uncertaint y in the dosimetry by a factor of three by experimentally calibrating the ionization chambers typically used in clinical practice. “Carbon-ion therapy is a cuttingedge alternative to conventional radiotherapy, which can benefit patients with deep-seated or radiation-resistant tumours,” says Oliver Jäkel from the German Cancer Research Centre (DKFZ) and the Heidelberg Ion-Beam Therapy Centre (HIT). “However, owing to its complexity, its use is not widespread, despite it being around for more than 20 years.” T he team, which includes researchers from the DKFZ and the HIT, along with the PhysikalischTechnische Bundesanstalt (PTB),

Physical Biology

Squeezing cells yields cancer clues Giving blood cells a gentle squeeze can reveal a great deal about their health, as researchers in France have shown in a new study published in Physical Biology. The research team used a tiny force probe to measure the mechanical responses of healthy and cancerous hematopoietic cells – biological structures that help to renew blood in the body – and found distinct differences in their physical characteristics. First, the scientists report that cells harvested from the bone marrow of five leukemia patients appeared much stiffer than comparable samples taken from five healthy volun-

Precision treatment The Heidelberg IonBeam Therapy Center.

were taken in the entrance channel of a scanned 6 × 6 cm radiation field consisting of carbon ions with an energy of 429 MeV per nucleon. These measurements allowed the team to experimentally determine the so-called kQ factor of the chambers, which is determined by the quality of the beam. “Because of the lack of experimental data, up to now, the kQ factor has been calculated,” comments lead author Julia-Maria Osinga-Blättermann from PT B and DKFZ. “Our result proves that experimental kQ factors with small uncertainties can be used instead.” The team was able to experimentally determine the kQ factor with a relative standard measurement uncertainty of 0.8%. “This is about a three-fold reduction of the uncertainty compared to calculated values, and thus allows us to significantly reduce the overall uncertainty related to ionizationbased dosimetry of clinical carbon ion beams,” Osinga-Blättermann concludes.

are aiming to improve the measurement and assessment of the absorbed radiation dose. “Contrary to the potential high precision of ion beams, the accuracy of the dosimetry for carbon ions has not, until now, been as good as for high-energy photon or electron beams,” says Jäkel. “We hope this study will provide a means to overcome that particular hurdle.” The research team, who reported their results in Physics in Medicine & Biology, directly calibrated the ionization chambers by using water calorimetry to measure the absorbed dose to water. The measurements Phys. Med. Biol. 62 2033

teers. The sensitivity of the atomic force microscope used in the study also enabled the group to identify areas of localized brittle failure accompanying the stiffening of the cancerous cells. “What makes this work so exciting is not simply seeing a difference between the stiffness of healthy and cancerous cells, but observing that the cancerous cells also lost their dynamic ductility and behaved as more breakable objects,” commented Françoise Argoul, who led the study and is a member of the French National Centre for Research (CNRS). T he me c h a n i c a l s i g n at u re s obtained by squeezing or deforming cells could help physicians to determine the presence of cancers such as leukemia in patients. Significantly, the mechanical data might also provide clues as to how long the cells have been affected by the disease.

Deformation data Healthy cells were analysed and results compared with cancerous cells.

“We would like to construct a hematopoietic cancer cell chart, where the loss of cell mechanical functions could be graded, depending on the leukemia and its stage of evolution,” explains Argoul. Argoul added that biopsy needles could, in principle, be adapted to allow local sensing of internal soft tissue structures, which would enable their use in a hospital setting. Before progressing to testing cells inside the body and preparing for clinical trials, the researchers must first build up sufficient information from their measurements on isolated cells under a range of conditions in the lab. Phys. Biol. 13 03LT01

13 M BIOSCI 0517-Cancer-p13-14.indd 15

23/06/2017 10:53

Biosciences: taking research from the lab to the clinic

Cancer diagnosis and therapy

ioppublishing .or g /biosciences

Physics in Medicine and Biology

Tomography sheds light on tumour progression Understanding tumour formation in the context of the tissue microenvironment is of critical importance to cancer researchers. Interactions between cells and the extracellular matrix influence tumour growth, and matrix crosslinking can facilitate the invasion and migration of tumour cells into healthy tissue. Studies to investigate the effect of these interactions have so far relied on in vitro tissue culture models, but a new technique – developed in a collaboration between tissue engineering and biophotonics researchers – offers a quick, quantitative and non-invasive approach to study the extracellular matrix and its host cells at the nanoscale. The technique, called inverse spectroscopic optical coherence tomography (ISOCT), exploits spectral information to extract ultrastructural parameters – specifically, the mass density correlation parameter D – that can be used to quantitatively characterize a sample. Previous studies have shown that ISOCT can

Probing tumour formation The bench-top ISOCT system.

crosslinking of collagen in the extracellular matrix, which in the tumour microenvironment is believed to be catalysed by the enzyme lysyl oxidase (LOX). They have also shown that an increase in D correlates with an increase in the proliferation of human colon cancer cells that had been seeded on a crosslinked collagen substrate. “T hese results poi nt toward ISOCT as a potential screening modality for colon cancer,” Graham Spicer from Northwestern University told medicalphysicsweb. "In order to further the application of ISOCT as a screening tool, our lab is currently developing an ISOCT probe that can be inserted into the rectum for imaging and measurement of D from rectal tissue. With further miniaturization, this probe could also find application in catheter-based imaging of arterial plaques or a needle-type probe for screening of cancer in other locations in the body.”

detect subtle changes in cancerous tissue through the measurement of small increases in D values, plus the technique is effective to depths of 1–2 mm and so enables rapid imaging of 3D cell cultures. In new research reported in Physics in Medicine & Biology, a US research team led by Vadim Backman of Northwestern University have shown that ISOCT can reveal

Phys. Med. Biol. 61 6892

Physics World Discovery

Over the last few decades, proton therapy has emerged from the research laboratory to become an increasingly popular technique for treating cancer. Proton Beam Therapy, a new ebook in the Physics World Discovery series, takes a close look at the physics of this cancer treatment; explores the benefits of using protons to target and destroy cancerous tumours; and examines the challenges associated with bringing this approach into the clinical mainstream. The ebook is written by Harald Paganetti, di rector of physic s research at Massachusetts General Hospital and professor of radiation oncology at Harvard Medical School. He is a pioneer in advanced Monte Carlo dose calculations for proton therapy, and is considered the world expert on the relative biological effectiveness of proton beams. “Proton therapy is becoming a standard treatment option but there are still many challenges in terms of

the physics, biology and clinical use of protons, which are summarized in this ebook,” Paganetti explains. There are currently around 60 proton therapy facilities worldwide, and their number is increasing rapidly – which makes this publication particularly timely. Proton pioneer The ebook serves as ideal intro- Harald Paganetti. ductory material for students or research fellows starting to work in proton therapy. “I have received very positive feedback so far,” says Paganetti. “There are books on proton therapy physics that are several hundred pages long and provide a comprehensive view. In contrast, this ebook gives a short overview that can Proton Beam serve as an introduction and readers Therapy can then consult other books to go into more detail.” Paganetti outlines the physics Harald Paganetti describes of proton beams and how this is the use of proton beams in the treatment and management exploited in radiation therapy, and he of cancer. also examines some of the challenges associated with the technique – rangphysicsworld Discovery ing from the technical issues involved

H Paganet ti

Proton therapy: the benefits and the challenges in setting up a clinical facility to ongoing research into the physics (dose and range uncertainties) and biology (toxicities and relative biological effectiveness) of this treatment modality. He finishes with a look forward. “Right now, only about 1% of radiation therapy patients are treated with protons, but that number is rapidly increasing due to an increased availability of proton facilities,” he explains. “I do think that the share of proton therapy in radiation therapy will increase. Clinical efficacy will play a role, as well as economic considerations. It is thus important that we engage in clinical trials to demonstrate the value of proton therapy for various disease sites.” • Proton Beam Therapy forms part of the Physics World Discovery series of short-form ebooks, which offer an insight into the latest hot topics in physics from leading voices and rising stars in physics. View the launch collection at physicsworlddiscovery.org.

14 M BIOSCI 0517-Cancer-p13-14.indd 13

23/06/2017 10:54

Biosciences: taking research from the lab to the clinic

Q&A: Simon Hattersley

ioppublishing .or g /biosciences

Physics World

Tracing the spread of cancer Simon Hattersley, co-founder of Endomagnetics, explains how technology that exploits magnetic nanoparticles can be used to detect cancer. How did Endomagnetics get started?

It came out of something called the Biomagnetometer Project, which was set up by Quentin Pankhurst at University College London (UCL). He was looking for applications of magnetic nanoparticles, and a surgeon, Michael Douek, told him that he and his colleagues would really like new tools to help them perform operations on breast-cancer patients. One idea they discussed was to use magnetic material to track lymph flow from the area around a tumour through to the lymph nodes, so that surgeons could biopsy the right nodes and thus determine whether a cancer had spread. This information is critical to providing correct treatment for the patient, as unnecessary surgery and chemotherapy can be almost as damaging as under-treatment. Existing techniques involved using a blue dye and a radioactive tracer that can be very difficult to obtain, and there’s also a lot of regulatory inconvenience associated with radioactivity. So there was clearly a possibility of using magnetic particles to do the localization instead, and Quentin managed to get a research grant to pursue this. That’s when I got involved.

How did the technology develop?

Our original system for detecting the magnetic nanoparticles was based on a superconducting quantum interference device (SQUID) sensor that operated in liquid nitrogen. But supplying liquid nitrogen to operating theatres during the clinical trials was a real nuisance. Also, SQUIDs are very sensitive to radio-frequency fields, and under certain circumstances they can become completely non-operative if there’s lots of background interference. That lack of robustness is just not acceptable for this sort of system, and eventually I found a way to perform our measurements with room-temperature electronics. To do this, I increased the frequency to boost sensitivity, used really low-noise amplifiers, and further developed our correlation techniques.

What other challenges did you overcome?

Initially, our focus was on building a machine that was sensitive enough to

paperwork that has to be produced for the FDA’s pre-market authorization: we had to have a special consultant in for three months, supported by two staff at Endomagnetics, and the result was something like two crates full of paper. But we are now looking at possibly getting approval by the end of 2017. Meanwhile, we do have another product that is already approved in the US – a tiny magnetic marker that can be injected into a patient by a radiographer, and subsequently found by a surgeon using our detection technology, days or months later as required. Simon Hattersley (right) with Quentin Pankhurst of UCL.

detect magnetic nanoparticles, but in late 2010 we learned there was a problem with the nanoparticles themselves. We were using a material called Endorem, which is an intravenously injected contrast agent for magnetic resonance imaging. But then other types of contrast agent, which are gadolinium-based and completely unsuitable for our purposes, took over the market. This was a bit of a blow, but our chief executive officer, Eric Mayes, tracked down the ultimate manufacturer of the nanoparticles and got an agreement to supply the particles we needed to our specification. He also got a CE mark for nanoparticles that could be injected into tissue. We’d been using the previous stuff “off-label”, which meant that we wouldn’t have been able to market it ourselves. And when you do the sums, it becomes quite obvious that it’s the consumable product that makes money for you, not the instrument itself. It’s like printers and ink – you make money out of the ink, not out of selling the printers.

What’s the next step for the company?

Our magnetic nanoparticles have been used to treat around 20 000 women so far, primarily in Europe, and we’ve recently been applying to get them approved by the US Food and Drug Administration (FDA). Getting approval for our product in Europe was actually not too bad, but the US process has been quite difficult. It is absolutely astonishing the amount of

What do you know now that you wish you’d known when you started?

I think we were a bit naïve about how the investment process works. The technology transfer departments of universities are quite often not really part of the university at all; although they tend to promote themselves as being there to “help researchers commercialize their ideas” (and that is true to an extent), they can take an extremely hard-nosed attitude. It’s not nearly as straightforward as it is sometimes painted, and developing medical devices and getting them to market is a long-winded process. Endomagnetics has actually gone extremely well in many ways. The other company I co-founded, Michelson Diagnostics, also has some really cracking technology; the main product is a skin imaging system that can detect skin cancers without the need for a biopsy. But we didn’t realize how difficult it would be to sell our imaging technology to clinicians, even with lots of research papers published to show how useful our system is. We are now developing alternative applications, in assisting the treatment of burns and scars, which we hope will be more successful.

Do you have any advice for anyone thinking of starting a new medical-device firm?

Talk to a lot of good people. It’s difficult to find the good people, but you can sniff them out eventually. There’s so much you need to know, frankly, so it’s very good to find some people who’ve been through it.

15 M BIOSCI 0517-Endomag Q&A-p15.indd 7

23/06/2017 10:54

Biomedical Physics & Engineering Express ™

ENDORSED BY

iopscience.org/bpex A broad, inclusive, rapid-review journal devoted to publishing new research in all areas of biomedical engineering, biophysics and medical physics, with a special emphasis on interdisciplinary work between these fields. Editor-in-Chief Robert Jeraj, University of Wisconsin, USA

To find out more about publishing your work in BPEX, visit iopscience.org/bpex

internals ads.indd 24

23/06/2017 11:40

Biosciences: taking research from the lab to the clinic ioppublishing .or g /biosciences

Analysis and diagnostics

Re s ea rcher s i n t he US have revealed the first results from the EX PLOR ER project, which is attempting to build world’s first positron emission tomography (PET) scanner capable of imaging the whole body. “The EXPLORER scanner will allow all tissues and organs to be imaged simultaneously, with 40 times more sensitivity than the current generation of clinical PET/CT scanners,” says Simon Cherry of the University of California, Davis, one of the partners in the multi-institutional project. PET is a molecular imaging technique used widely in clinical diagnostics and research to observe metabolic processes and molecular pathways in the body. Current systems can only scan specific parts of the body at any one time, which limits their use and does not make best use of the radiation doses involved. “The vision for the EXPLORER project is to solve two fundamental limitations of PET as it is currently practiced,” continues Cherry. “The

E XPLORER Project

Towards the first full-body PET scanner

Full-body scanning An artist’s rendering of the EXPLORER fullbody PET scanner.

struction method with quantitative correction, and used Monte Carlo simulations to evaluate the quality of the resulting images. “In essence, what we aimed to do was test if it possible to efficiently process all the data generated from the half a million detectors needed for a total-body scanner,” explained Ramsey Badawi, another project coleader. The team used computer simulations to evaluate the image quality that could be achieved with the reconstruction algorithm, and compared the performance of the EXPLORER with a current clinical scanner. These simulations showed the EXPLORER could reach superior performance for total-body PET imaging at very low radiation doses, with a six-fold increase in signal-tonoise ratio compared with the current scanner. “Our simulations show EXPLORER will enable PET imaging studies of the whole body to be performed using 1/40th the radiation dose, or in 1/40th of the time (potentially in a single breath-hold), or with 40-fold better signal,” says Badawi.

first is to allow us to see the entire body all at once. The second is that we’re collecting almost all of the available signal, which means we can acquire higher-quality images, or collect the same images as today’s scanners much more quickly or at a much lower radiation dose.” R u n n i n g a t f u l l c a p a c i t y, EXPLORER could generate around 40 terabytes of data every day, posing a huge computational challenge for data handling and image reconstruction. In these first results, published in the journal Physics in Medicine & Biology, the team has developed an efficient, quantitative image recon- Phys. Med. Biol. 62 2465

Methods and Applications in Fluorescence

Green light for photodynamic diagnosis Researchers in Denmark have demonstrated that a high-power LED light source operating at 525 nm could improve the detection and treatment of cancerous tumours in the bladder. When integrated into equipment that is routinely used in both outpatient departments and the operating theatre, the purposebuilt light source has been shown to improve the results from a technique called photodynamic diagnosis (PDD), which is commonly used in the treatment of bladder cancer. PDD works by detecting a bright red f luorescence produced by tumour cells when they come into contact with a particular amino acid, which is administered to the patient before the treatment. Current PDD techniques exploit blue light at around 430 nm to excite this red fluorescence, but it has the

unwanted side-effect of also generating green fluorescence from urine in the bladder. This makes it difficult to pinpoint the location of the tumours during endoscopic surgery. In the new study, reported in Methods and Applications in Fluorescence, Lars Lindvold of the DTU Centre for Nuclear Technologies in Roskilde and Gregers Hermann of the Herlev/ Gentofte Hospital in Copenhagen show that their purpose-designed light source significantly reduces the green fluorescence from urine. And the longer wavelength of the LED light source is also able to induce natural fluorescence from healthy bladder tissue, which is used during surgery to image the bladder. Existing systems are fitted with a second white light source to generate this natural fluorescence, which means that the surgeon must switch

Lighting up A green LED light source can reveal tumours in the bladder (left) and can also allow surgeons to see the bladder tissue during surgery (right).

between blue and white light to perform diagnosis and surgery. Only one setting is required with the new light source, which means that the surgeon can view the inside of the bladder at the same time as the location of the tumours. “It is important to emphasize that the results presented in this paper are to be regarded as a proof-of-principle,” the authors conclude. “Based on the observations reported in this paper, a series of experiments will be needed to prove the efficacy of the new method in order to establish a proper protocol for this method in the clinic, including a study of a larger cohort of patients.” Methods Appl. Fluoresc.4 045002

17 M BIOSCI 0517-Analysis diagnostics-p17-18.indd 17

23/06/2017 11:00

Biosciences: taking research from the lab to the clinic

Analysis and diagnostics

ioppublishing .or g /biosciences

Journal of Breath Research

Canine diagnosis put to the test Reports of dogs sniffing out cancer in humans have offered the hope that animals could warn of the disease in its early stages. However, new results published in Journal of Breath Research indicate that canine scent detection might not be as powerful as might be expected when dogs are deployed in a real screening situation. To provide samples for the dogs to test, researchers in Austria and Germany recruited 122 volunteer patients: 29 of the subjects had been diagnosed with lung cancer, but were not yet treated, and the remaining 93 subjects had no signs or symptoms of the disease. In the screening programme designed by the group, breath samples obtained from the volunteers were presented to six highly trained sniffer dogs in a double-blind manner to eliminate any subjective bias from the trial. The dogs detected 78.6% of the positives correctly, but only 34.4% of the negatives. “Our dogs made mistakes with both positive and negative samples, and I think that one important reason

for the inferior results might be that a true double-blind situation puts a lot of stress on the animals and their handlers,” commented Klaus Hackner from Krems University Hospital in Austria, one of the institutions taking part in the study. “Success and regular rewards are important for every kind of sniffer detection work.” A ll of the animals in the dog squadron had experience of finding buried people or as avalanche dogs in the Austrian mountains, and were considered capable of learning a new scent for detection. To prepare them for the study, the dogs were trained for six months in advance with a total of 150 training samples. These vials consisted of lung-cancer breath samples and healthy controls based on the same inclusion criteria as the test samples. Hackner believes that there is scope to improve on the results with the right protocol: one that provides the dogs with more regular rewards to keep them motivated and in good spirits. “This disparity is not likely to

Physics in Medicine & Biology

Magnetic imaging captures beating heart Researchers at the University of Würzburg in Germany have produced a dynamic scan of a mouse’s beating heart by using new variant of magnetic particle imaging (MPI). The new technique, called travelling wave MPI (TWMPI), exploits an array of magnetic field coils to create a dynamic field gradient and produce a large enough field-of-view (FOV) to scan an entire mouse. MPI, which promises sensitive, fast, and quantitative imaging for both pre-clinical and clinical applications, works by mapping the distribution of superparamagnetic iron oxide nanoparticles in the body. This mapping is achieved by measuring the particles’ radio-frequency response to an oscillating magnetic field, which is applied on top of a magnetic field gradient that saturates the particles’ magnetization. The first MPI systems used permanent magnets to generate a static

MPI masters Group leader Volker Behr and first author Patrick Vogel.

Dog detective Can highly trained sniffer dogs detect cancer?

be a detection issue; dogs have been shown to have extremely sensitive noses as proven by their use in tracking, bomb detection, and search and rescue,” he explains. “However, in contrast to analytical instruments, dogs are subject to boredom, limited attention span, fatigue, hunger, and external distraction.” Even with modifications to the protocol, questions remain on whether dogs are a practical solution to providing early warning of major diseases. Ideally, cancer screening should be quick, easy and affordable. For these reasons, the pursuit of an electronic device for sniffing out cancer – a so-called “e-nose” – remains high on the agenda. J. Breath Res. 10 046003

The TWMPI system was able to acquire data for a single 7 mm coronal slice over 10 seconds at 20 frames per second. The MPI signal strength fluctuated as the heart emptied and filled with nanoparticles, and the researchers were able to use this information to produce an accurate measurement of the mouse’s heart rate. “The results show that the TWMPI scanner is sufficiently fast and sensitive to determine the distribution of an iron oxide tracer,” said Vogel. “For us it is a very important step, said Volker Behr, MPI group leader at Würzburg. “We demonstrated that the TWMPI approach is an alternative MPI scanner design that is able to work at the same level as other MPI systems.” The group is now optimizing individual hardware components in the TWMPI system and improving the system's image reconstruction algorithm. They also plan to develop multimodal scanners that would combine MPI with magnetic resonance imaging or computer tomography, which will be important for MPI to be routinely used for pre-clinical and clinical imaging.

field gradient, but their FOV was only large enough to image individual organs in mice. The new TWMPI technique overcomes this problem by creating a dynamic field gradient, and in a new study reported in Physics in Medicine & Biology, the researchers have demonstrated in vivo images of a beating mouse heart. The researchers improved the basic line-scanning TWMPI configuration to enable the system to acquire a two-dimensional data slice in a single trajectory. “This mode can scan an entire slice out of the FOV within the same time as one line using the linescanning mode,” said first author Patrick Vogel. “This makes this mode very fast, up to almost 2000 frames per second.” Phys. Med. Biol. 61 6620

18 M BIOSCI 0517-Analysis diagnostics-p17-18.indd 18

23/06/2017 11:01

Biosciences: taking research from the lab to the clinic ioppublishing .or g /biosciences

Biophysics

Liquid breathing moves a step closer Liquid ventilation – breathing a liquid instead of air – has long been the stuff of science fiction. But researchers have recently started to test its efficacy for treating severe pulmonary or cardiac trauma, plus it also has potential applications in deep diving and space travel. Despite this growing interest, very little is known about the long-term outcome of liquid ventilation, as well as other key parameters such as the volume of liquid that is breathed in and out. Now, however, Thomas Janke and Katrin Bauer at TU Bergakademie Freiberg in Germany have devised a new technique to visualize the effect on the human body. “In clinical liquid ventilation, the lung is filled with liquid, rather than air,” explained Janke. “The liquid perfluorocarbon (PFC), which is used for liquid ventilation, has proven perfectly suitable as a breathing medium, as it not only dissolves high amounts of oxygen but also acts as anti-inflammatory for human tissue.”

Every breath you take Liquid ventilation could be used in deep diving as well as other applications.

the average oxygen concentrations in the liquid entering or leaving the body. In the study, which was reported in Measurement Science and Technolog y, the researchers developed a “sensor liquid”, which incorporates a fluorescent dye that exhibits higher fluorescence at low oxygen concentrations. By introducing the sensor liquid into an in vitro model of the human lung’s bronchial tree, the researchers were able to measure the fluorescence – and thus the oxygen concentration – as the liquid flowed through the model. T h is te ch n ique a l lowed the researchers to map the absorption and transport of oxygen, and also revealed distinctive concentration patterns during inspiration and expiration. “Our results showed high potential for this technique to visualize the oxygen transport in a human airway model,” concludes Bauer. “We now plan to employ the same technique to look at more complex and realistic human airways.”

The challenge for Janke and Bauer was to measure how much oxygen is transported into the body’s airways during liquid ventilation, since previous techniques could only monitor Meas. Sci. Technol. 28 055701

Journal of Physics D: Applied Physics

Molecular movements in biomembranes Researchers working at the interface between biophysics and cell biology are focusing much of their at tent ion on c el l membra ne s , since important processes such as adhesion, signalling and recognition exploit the properties of the two-dimensional membrane matrix. In fact, about one third of the eukar yotic genome encodes proteins found in cell membranes, suggesting that the membrane is a crucial site for protein-protein interactions. A recent special issue of Journal of Physics D: Applied Physics attempts to capture the latest experimental and theoretical research into the movements of molecules in biomem-

branes. Guest editors Eugene Petrov of the Max Planck Institute of Biochemistry in Martinsried, Germany, and Gerhard Schütz of TU Wien in Austria have brought together review articles and original studies of both model membrane systems and live cell membranes. “Recent research has revealed that there is a variety of ingredients that modulate molecular movements in the membrane,” write Petrov and Schütz in their introduction. “We believe that this special issue provides a timely overview over the current concepts and questions about the movements of membrane constituents, and we wish you an exciting and entertaining read.”

SOME ARTICLES IN THIS ISSUE Convergence of lateral dynamic measurements in the plasma membrane of live cells from single particle tracking and STED-FCS B Christoffer Lagerholm et al J. Phys. D: Appl. Phys. 50 063001 Monte Carlo simulations of protein micropatterning in biomembranes: effects of immobile sticky obstacles Andreas M Arnold et al J. Phys. D: Appl. Phys. 49 364002 Effect of anchor positioning on binding and diffusion of elongated 3D DNA nanostructures on lipid membranes Alena Khmelinskaia et al J. Phys. D: Appl. Phys. 49 194001

19 M BIOSCI 0517-Biophysics-p19-20.indd 18

23/06/2017 11:01

Biosciences: taking research from the lab to the clinic

Biophysics

ioppublishing .or g /biosciences

New Journal of Physics

Modelling reveals bacteria behaviour Bacteria assemble Simulations show how bacteria spread infection.

Physiological Measurement

Stay connected Network physiology is an emerging research field that aims to understand and organs dynamically interact and complex interactions integrate,” says Plamen Ch Ivanov in the human body.

most commonly used antibiotics,” said lead author Wolfram Pönisch from the Max Planck Institute for the Physics of Complex Systems. “Our study aimed to discover how the pili govern the formation and dynamics of these microcolonies, which is still not well understood. N. gonorrhoeae relies on pili to move, and to form microcolonies consisting of several thousand cells, which made it an ideal model.” The team believes that this is the first computational model of microcolonies consisting of single cells interacting mechanically via individual pili. “Understanding this could lead to a better knowledge

Focus on network physiology The human body is an integrated network of complex systems that continuously interact to produce distinct physiologic states, such as consciousness and unconsciousness. Any breakdown in communications across the network can lead to dysfunction of individual systems or breakdown of the entire physiologic network, as seen in conditions such as sepsis, coma and multiple organ failure. The emerging field of network physiology aims to understand the interactions between the organs and different physiological systems within the body. “Despite their importance to basic physiology and clinical practice, we do not know the principles and mechanisms through which diverse physiological systems

from Boston University and Harvard Medical School, who is guest editing a focus issue on network physiology in the journal Physiological Measurement. “Identifying and quantifying the network of physiologic interactions between diverse integrated organ systems is a major challenge – and one that network physiology aims to address.” Ivanov believes that the focus issue will provide a forum for medical specialists and clinical practitioners, along with researchers specializing in biomedical engineering, signal processing, nonlinear dynamics and statistical physics, to discuss new methodologies and

of the gonorrhoea infection, as the microcolonies of N. gonorrhoeae are the infectious units of the disease,” says co-author Vasily Zaburdaev. “Hopefully, this work will enable the development of new ways to control the formation of colonies and limit the spread of the infection.” The researchers believe that the model can also be applied to other bacteria, including N. meningitidis – the bacteria that may cause meningitis. “We may be able to discover how that bacteria behave and, potentially, work towards new and more effective treatments for it as well,” says Zaburdaev. New J. Phys. 19 015003 Plamen Ch Ivanov

A new study into how bacteria move, behave, and form colonies could allow a better understanding of infections, and pave the way to new antimicrobial treatments. In the study, published in the New Journal of Physics, an interdisciplinary team from the Max Planck Institute and Helmholtz-Center, Dresden, and from Brooklyn College of the City University of New York, used multiscale computer modelling to reveal how bacteria use pili – hair-like structures extending from the bacteria’s surface – to spread the infection. The team studied the Neisseria gonorrhoeae bacteria, the cause of one of the most common sexually transmitted diseases – gonorrhoea. Their simulations show how the bacteria use pili to self-assemble into microcolonies and, eventually, biofilms. Such biofilms are a major concern in medical and engineering applications, since the bacterial infections they cause are often much less responsive to antimicrobial treatments, and so it is critically important to understand how they form and grow. “Over the past 20 years, there has been an alarming increase in reported gonorrhoea cases where the bacteria were resistant to the

theoretical frameworks in network physiology. He hopes that the issue might also trigger the development of new databases of continuous and synchronous recordings of multiple physiological parameters, and promote data-driven discoveries of the basic physiologic laws and control mechanisms that underpin physiologic interactions. The focus issue, which is entitled “The new field of Network Physiology: redefining health and disease through networks of physiological interactions”, is now open for submissions and will remain so until December 2017.

20 M BIOSCI 0517-Biophysics-p19-20.indd 19

23/06/2017 11:02

Biosciences: taking research from the lab to the clinic ioppublishing .or g /biosciences

News from IOP Publishing

Biophysical Society partners on ebooks The Biophysical Society and IOP Publishing have forged a new publishing partnership to create a comprehensive collection of ebooks that will support the development and dissemination of knowledge in biophysics. The collaboration will combine the world-leading expertise and domain knowledge of the Biophysical Society with IOP’s innovative ebooks programme, with the aim of building a library of valuable content for this expanding research community. The joint ebooks programme will publish textbooks, monographs, reviews, and handbooks covering all areas of biophysics research. Subject coverage will include everything from bioengineering and biological fluorescence through to molecular biophysics and membrane structure and assembly. “The Society leads the development and dissemination of knowledge in biophysics, and this vision for a new collection of books developed and written by the community, for the community, absolutely supports our core mission.” commented Rosalba Kampman, executive officer of the Biophysical Society. “Collaborating closely with IOP Publishing, a society

publisher that holds values in common with our own, will be an effective way to deliver this initiative to our members and the broader biophysics community.” Commissioning is already underway, with the first titles due be published in 2019. The programme will be guided by an editorial advisory board, comprising selected subject experts who will identify key areas of interest for the Biophysical Society’s members and the wider community. “We are delighted to be partnering with the Biophysical Society in this exciting endeavour,” commented Jeff Lewandowski, senior publisher at IOP Publishing. “By combining our experience in ebooks publishing with the expertise and reputation of the Biophysical Society, this collaboration will disseminate biophysics knowledge globally, and deliver impact, recognition and value to the scientific community.” The new ebooks will be available in multiple formats, including HTML, PDF, EPUB 3, and MOBI for Kindle, with options for multimedia and mathML. The series will be hosted on IOPscience, a platform that helps readers to discover relevant content

Creating a library to define biophysics

across both ebooks and journals. There are no restrictions on concurrent usage, while print-on-demand options will also be available. ● If you would like to be part of this programme, please contact [email protected] to find out more and to submit a book proposal.

Peer review under the spotlight Since the beginning of the year, IOP Publishing has been testing the merits of so-called double-blind peer review, in which the referee does not know who has submitted the article. Authors submitting papers to two journals – Biomedical Physics & Engineering Express and Materials Research Express – now have the option of choosing double-blind review or the more conventional single-blind approach, where the authors don’t know the identity of the reviewer, but the reviewer knows who has submitted the article. The response from the community has been positive so far, with

Biomedical Physics & Engineering Express ™

iopscience.org/bpex ENDORSED BY

NEW FOR 2017 Double-blind peer-review option

Materials Research Express ™

mrx.iop.org

NEW FOR 2017 Double-blind peer-review option

around one in five authors choosing the double-blind option when submitting to both journals. The pilot scheme will run until the end of 2017, and during that time IOP Publishing will be monitoring the take-up rate of the double-blind option, authors’ satisfaction with the process, and any effects on overall publication times. “We’re keen to find out as much as we can about what our authors, reviewers and the wider research community think of the double-blind option,” said Simon Harris, one of three managing editors who oversee the peer-review process at IOP Publishing. “At the end of the year-long pilot, we’ll let the community know what we’ve learned, and whether or not we plan to continue with the double-blind option on our journals.”

21 M BIOSCI 0517-News from IOP-p21-22.indd 21

23/06/2017 11:03

Biosciences: taking research from the lab to the clinic

News from IOP Publishing

ioppublishing .or g /biosciences

Discover more with Physics World ebooks Outstanding Reviewer

2016

Space Weather

The Dark Universe

Quantitative Finance

Complex Light

Proton Beam Therapy

Mike Hapgood introduces the physics of space weather, and how ongoing research is helping to mitigate its risks for critical infrastructures on Earth.

Catherine Heymans presents the cosmological toolkit of observations to uncover the nature of dark matter and dark energy.

Jessica James describes the development of the mathematics of finance and the contributions that physicists have made to it.

Jeff Secor, Robert Alfano and Solyman Ashrafi review the fundamental physics and the burgeoning applications of complex light beams.

Harald Paganetti describes the use of proton beams in the treatment and management of cancer.

physicsworld Discovery

Rewards for reviewers Two new initiatives have been introduced by IOP Publishing to highlight and recognize the vital role that expert reviewers play in scholarly communications. The first is a new partnership with Publons, a reviewer recognition service that integrates with the Scholar One submission system to enable referees to track, verify and showcase the reviews they submit to IOP Publishing journals. Reviewers for participating journals have the option to add a verified record of each review to their Publons profile, even if the manuscript is never published. Since IOP Publishing introduced the option at the end of 2016, more than 1200 referees have recorded their reviews with Publons – which suggests there is demand for this type of service. By default, only the name of the journal and the year of the review are displayed on Publons to protect the anonymity of the reviewer. This year also sees the introduction of IOP Publishing’s Reviewer Awards, designed to celebrate the contributions of the very best reviewers across the previous year. The editors of each journal have selected one person to receive the Reviewer of the Year Award, based on the quality, quantity and timeliness of their reports, while a number of other excellent referees have been recognized with Outstanding Reviewer awards. All the award winners are listed in full on the individual journal pages on IOPscience. More than 1400 of the 27,000 researchers who reviewed for IOP last year received an award.

physicsworld Discovery

physicsworld Discovery

physicsworld Discovery

physicsworld Discovery

The first titles in a new series of Physics World Discovery ebooks are now published and free to read on IOPscience. These short-form ebooks – written by leading voices from the scientific community, and commissioned and edited by Physics World’s award-winning journalism team – offer readers an accessible and authoritative introduction to some of the most exciting topics in physics. “This is an exciting experiment that allows authors to work directly with our science journalists to create engaging material that helps readers of all levels to understand the importance of research in the physical sciences, and how it connects to broad societal issues,” said Jamie Hutchins, publishing director at IOP Publishing. “Physics World Discovery is straightforward for authors to write, ensures rapid publication times, and allows an interested reader to grasp new concepts and trends quickly.” The first five publications in the Physics World Discovery collection

showcase a range of diverse and fast-moving research areas, spanning quantitative finance, protonbeam therapy, complex light, space weather, and the dark universe. More titles will be added during the year, including one on the medical applications of particle physics. “The Physics World Discover y series provides exciting and accessible material to educate students and others about the latest challenges in fast-moving research fields,” said Professor Catherine Heymans of the University of Edinburgh, the author of The Dark Universe. “Thanks to Physics World’s reach and strong reputation for presenting physics in a way that is easy to understand, I was delighted to contribute to the Discovery series by writing about observational techniques to study dark matter and dark energy. I recommend this new series whole-heartedly.” ● View the Physics World Discovery collection at physicsworlddiscovery. org.

From acceptance to online in 24 hours

are also be indexed in PubMed as “ahead of print”. The DOI remains the same when the final version of record is published, and the PubMed status is also updated at this time. To take advantage of this service, authors must complete and sign a copyright and publication agreement, and also confirm that they have all permissions needed to include any third-party content. Authors can opt out of accepted manuscripts if they wish. When planning some promotional activity, for example, it can be useful to delay publication to allow time for the material to be prepared, or to maintain an embargo period for journalists. Also, researchers currently engaging in IP or patent applications may wish to opt out of accepted manuscripts. ● For more information, and to find out which journals are offering accepted manuscripts, visit iopscience. org/accepted-manuscripts.

IOP Publishing has introduced new processes to allow the accepted version of the manuscript to be made available online just 24 hours after acceptance. At this early stage, the manuscript is provided as a flat PDF with the figures and formatting as provided by the author, and then the manuscript is replaced with the final published version once the article has been typeset and language-edited by specialist production editors. Once available online, the accepted manuscript is assigned a DOI and some basic information is provided about the article, including author name and affiliations where available. This information is registered with CrossRef and indexed by Google for discoverability, while relevant papers

22 M BIOSCI 0517-News from IOP-p21-22.indd 22

23/06/2017 11:04

Biosciences: taking research from the lab to the clinic ioppublishing .or g /biosciences

Adding value to IOP authors

medicalphysicsweb, the leading online resource for biomedical physicists and engineers, offers extra visibility for some of the best papers published in IOP journals. As part of its remit to report on the latest advances in fundamental research, emerging technologies and clinical applications, medicalphysicsweb regularly features the work of authors who publish their research with IOP, it now also covers biophysics and bioengineering alongside its core focus on radiation oncology. Visit medicalphysicsweb.org to get the latest updates and to sign up for the regular newswire.

IOP automatically uploads all papers funded through the National Institutes of Health (NIH) to PubMed Central, unless an author requests otherwise. This service supports the NIH’s Public Access Policy, which requires all North American authors to make NIH-funded research publicly available in PubMed Central no later than 12 months after online publication. To comply with this policy, North American authors should highlight any NIH funding, including the grant number, in the acknowledgments section of the manuscript.

IOP Editing Services has partnered with Editage to offer authors comprehensive support for manuscript preparation, including English-language editing, translation services, plagiarism checking and a technical review service. The service will be available to all authors, regardless of where they wish to publish, and a range of pricing and delivery options are available. Each manuscript received by IOP Editing Services will be assigned to an editor or translator who specializes in the relevant discipline, and a stringent two-level check will ensure that the edited manuscript meets international publication standards. Visit http://iopeditingservices.editage. com for more information.

Accepted manuscripts In response to feedback from researchers, IOP Publishing is launching a new service to allow accepted articles to be made available online within 24 hours. This offers multiple benefits for our authors and readers, allowing research to be accessed and cited earlier than ever before. Visit iopscience.org/accepted-manuscripts for more information.

Article level metrics allow authors to monitor the wider impact of research articles published in IOP’s journals. The tools provide articlelevel information on the number of downloads and citations, as well as shares and bookmarking through social media. All the data are updated on a weekly basis, and can be accessed from the abstract page by any article on IOPscience.

As part of IOP’s commitment to engage closely with our research communities and to meet their future needs, we are pleased to be offering authors the choice of single- or double-blind peer review on Materials Research Express from January 2017. Feedback from the research communities we serve suggests that there is a growing demand for the doubleblind review option (in which the reviewer does not know the identity of the author), and through this pilot scheme we aim to gain specific insight into uptake in the broad area of materials science. We look forward to communicating conclusions and outcomes of the pilot from the end of 2017.

SUPPORTING OPEN ACCESS

PE

N ACCES

All biosciences journals published by IOP Publishing offer open-access publishing options. As an author there are two main routes to making your article available on an open access basis, commonly known as green and gold open access. IOP offers authors both options to help best meet the needs of your personal circumstances. S

O

Gold When you select gold, an article publication charge is paid in return for full immediate open access to the version of record of your article. Many university and funder policies on open access have a requirement for authors to publish under a CC BY licence. All articles published on a gold open access basis with IOP Publishing use this licence as standard.

Green When you decide to follow the green route you are able to place the accepted version of your article into an institutional or subject repository after a 12-month embargo period (with some reuse restrictions). Whichever option you choose, you can be confident that you can continue to publish your work in top-quality journals, while also meeting the requirements of funder and university policies on open access. Referee rewards to help pay for gold open access IOP has a referee reward scheme in place that offers referees a 10% credit towards the cost of publishing on a gold open access basis every time you review an article for one of IOP’s journals.

23 M BIOSCI 0517-Adding value-p23-24.indd 23

23/06/2017 11:13

Biosciences: taking research from the lab to the clinic

Adding value to IOP authors

ioppublishing .or g /biosciences

Biosciences hits the headlines As part of our ongoing commitment to help gain recognition for authors and their work, we regularly highlight published articles to the news media, resulting in a broad range of print, online and broadcast coverage. Here are just a few examples of biosciences articles published in IOP Publishing journals that have made the headlines: HEADLINE ARTICLES Bee grooming behaviour could help with microelectromechanical cleaning A study on how bees groom has given new insight into the process of pollination, and could have implications for future microelectromechanical systems. Researchers examined how pollenating insects that purposely cover themselves with millions of pollen particles get clean enough to fly. It was covered in: • New York Times • Sydney Morning Herald • Brisbane Times • Quartz Guillermo J Amador et al 2017 Bioinspir. Biomim. 12 026015 Researchers measure vortex breakdown in a bird’s wake for the first time – thanks to 3D printed goggles New research has shed light on how the breakdown of strong vortices birds create by flapping their wings limits our ability to calculate the lift they generate to fly. Using a high speed laser, 4 cameras, and a parrotlet called Obi, engineers at Stanford University studied the tip vortices the bird generates to stay in the air. It was covered in: • Wired • Tech Times • The Times • Science magazine • Popular Science • Gizmodo Eric Gutierrez et al 2017 Bioinspir. Biomim. 12 016004 Researchers move a step closer to first full-body PET scanner Researchers from UC Davis revealed the first results from the EXPLORER project –which aims to build world’s first full total-body positron emission tomography (PET) scanner. Current systems are limited in the area of the body they can scan at any one time, which does not make best use of the radiation doses involved. The EXPLORER project aims to solve this. It was covered in: • Science magazine • The Scientist • Laboratory Equipment • Scientist Live Xuezhu Zhang et al 2017 Phys. Med. Biol. 62 2465

Guides for authors, referees and copyright Introductory guide for authors

Introduction to copyright and licensing

iopscience.org/referee-guide

iopscience.org/copyright-guide

FAQs / PUBLISHING GLOSSARY

PROMOTING YOUR PUBLISHED WORK / COPYRIGHT AND ETHICAL INTEGRITY

REVISING AND RESPONDING TO REFEREE REPORTS / ACCEPTANCE AND PUBLICATION

PEER REVIEW PROCESS

WRITING AND FORMATTING

iopscience.org/author-guide

CHOOSING WHERE TO SUBMIT YOUR PAPER

authors.iop.org

INTRODUCTION / CONTENTS

Introductory guide for authors

Introduction to refereeing

24 M BIOSCI 0517-Adding value-p23-24.indd 24

23/06/2017 11:13

Convergent Science

Physical Oncology Inviting submissions from the community Convergent Science™ Physical Oncology (CSPO) is the first interdisciplinary journal dedicated to integrating physical sciences with cancer biology and clinical oncology to advance our understanding and treatment of cancer in patients. The journal brings together all researchers in the field of physical oncology to address the major questions and barriers in cancer research. First issues of CSPO are now live on iopscience.org/cspo and will be free to read throughout 2017.

Founding editors

• Carole Baas, National Cancer Institute, Irving, TX, USA • Kelly Bethel, Scripps Clinic, La Jolla, CA, USA • Peter Kuhn, University of Southern California, CA, USA • Jorge Nieva, University of Southern California, CA, USA Visit iopscience.org/cspo to find out more about publishing your work in CSPO.

internals ads.indd 25

23/06/2017 11:36

Biosciences: taking research from the lab to the clinic

IOP journals in the biosciences

ioppublishing .or g /biosciences

The biosciences portfolio includes more than 20 journals, as well as award-winning journalism and ebook programmes, dedicated to providing the community with essential content covering all areas of bioscience. We offer a range of publication options to suit your needs, and once published, we will ensure that your work gets the attention it deserves.

Oncology Medical physics

Bioprinting

Biomedical engineering

Physiology

biosciences

Diagnostics

Biomimetics

Biophysics

Neuroscience

Nanomedicine

Biophotonics Biomaterials

Discover our full range of titles and guidance on how to submit your work at ioppublishing.org/biosciences. 26 M BIOSCI 0517-Journals-p26-27.indd 26

23/06/2017 11:14

Biosciences: taking research from the lab to the clinic

IOP journals in the biosciences

ioppublishing .or g /biosciences

To find out further information about our biosciences journals, visit ioppublishing.org/biosciences Biofabrication™

Convergent Science™

Physical Oncology

NEW FOR 2015

iopscience.org/cspo

Impact Factor: 5.240

Convergent Science™ Physical Oncology

Methods and Applications in Fluorescence™

The first multidisciplinary journal for researchers working in the field of physical oncology

Impact Factor: 2.656

Bioinspiration & Biomimetics™

Journal of Breath Research™

Impact Factor: 2.939

Impact Factor: 4.318

Biomedical Materials™ Impact Factor: 2.469

ISSN 1741-2560

JOURNAL OF NEURAL ENGINEERING Volume 12 Number 1 February 2015

Journal of Neural Engineering™

Physical Biology™ Impact Factor: 1.494

Physics in Medicine & Biology iopscience.org/pmb The international journal of biomedical physics published by IOP Publishing on behalf of the Institute of Physics and Engineering in Medicine

ISSN 0031-9155

Volume 61 Number 7 7 April 2016 TOPICAL REVIEW Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success Brian W Pogue, Jonathan T Elliott, Stephen C Kanick, Scott C Davis, Kimberley S Samkoe, Edward V Maytin, Stephen P Pereira and Tayyaba Hasan

Physics in Medicine & Biology

Impact Factor: 3.465

Impact Factor: 2.742

Journal of Radiological Protection

Physiological Measurement

Impact Factor: 1.657

Impact Factor: 2.058

iopscience.org/jne Featured articles Chemical stimulation of rat retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis S AMSOON I NAYAT, C OREY M R OUNTREE, J OHN B TROY AND L AXMAN S AGGERE Ten-dimensional anthropomorphic arm control in a human brain−machine interface: difficulties, solutions, and limitations B WODLINGER , J E D OWNEY, E C TYLER-K ABARA , A B S CHWARTZ, M L B ONINGER AND J L C OLLINGER

LA UN CH

Launch Issue – March 2015

W

iopscience.org/bpex

NE

Biomedical Physics & Engineering Express

Biomedical Physics & Engineering Express™

Other relevant journals • Applied Physics Express • EPL • Journal of Optics™ • Journal of Physics: Condensed Matter ™

• Journal of Physics D: Applied Physics™ • Methods and Applications in Fluorescence™ • Nanotechnology ™

• New Journal of Physics • Plasma Sources Science and Technology ™ • Reports on Progress in Physics™ • Smart Materials and Structures™ • Translational Materials Research™

27 M BIOSCI 0517-Journals-p26-27.indd 27

23/06/2017 11:14

®

LIGHT SOURCES Introducing the Lambda 421 Optical Beam Combiner, a newly patented concept for combining separate light sources with different spectra into a single output beam. We have a wide selection of high-powered LEDs, the highly stable Lambda XL plasma light source and Lambda LS Xenon arc lamp. WAVELENGTH SWITCHING & SHUTTERING A broad line of robust and reliable wavelength switching products including the Lambda 10-3 controller which controls of up to 3 wheels and 2 shutters. For tunable filters, single and 5-position filter changers provide access to any center bandpass from 338 to 900nm in nanometer increments. Our SmartShutter® offers the most sophisticated shutter control available.

MICROSCOPES Perform in vivo and in vitro advanced optical experiments using the MOM® 2-photon resonant scanning microscope, BOB open architecture upright scope, or SOM® simple moving microscope. We have solutions for wide field functional imaging, multi-photon imaging, photostimulation and slice electrophysiology. Stand-alone components include MScan software suite, the RESSCANNER, an ultra quiet resonant scan box and controller, and PS-2 PMT power supply.

NSOM TIPS Sutter Instrument, the recognized leader in micropipette fabrication technology, offers leading edge technology in the P-2000 micropipette puller, which allows for fast and repeatable nanospray tip production with complete control of tip morphology. The P-2000 can be pre-programmed to produce tips to your specifications at no extra charge.

Precision Instrumentation for the Sciences ONE D I G I T A L D R I V E , N O V A T O , CA. 94949 | PHONE: +1 415.883.0128 | FAX: +1 415.883.0572 EMAIL: [email protected] | WWW.SUTTER.COM

OPTICS SUPPLEMENT FULL_05_02_17.indd 1

5/2/17 10:15 AM