Tag Archives: organ-on-a-chip

Placenta-on-a-chip for research into causes for preterm birth

Preterm birth (premature baby) research has received a boost with this latest work from the University of Pennsylvania. A July 21, 2016 news item on phys.org tells us more,

Researchers at the University of Pennsylvania have developed the first placenta-on-a-chip that can fully model the transport of nutrients across the placental barrier.

A July 21, 2016 University of Pennsylvania news release, which originated the news item, provides more detail about the chip and the research (Note: Links have been removed),

The flash-drive-sized device contains two layers of human cells that model the interface between mother and fetus. Microfluidic channels on either side of those layers allow researchers to study how molecules are transported through, or are blocked by, that interface.

Like other organs-on-chips, such as ones developed to simulate lungs, intestines and eyes, the placenta-on-a-chip provides a unique capability to mimic and study the function of that human organ in ways that have not been possible using traditional tools.

Research on the team’s placenta-on-a-chip is part of a nationwide effort sponsored by the March of Dimes to identify causes of preterm birth and ways to prevent it. Prematurely born babies may experience lifelong, debilitating consequences, but the underlying mechanisms of this condition are not well understood due in part to the difficulties of experimenting with intact, living human placentae.

The research was led by Dan Huh, the Wilf Family Term Assistant Professor of Bioengineering in Penn’s School of Engineering and Applied Science, and Cassidy Blundell, a graduate student in the Huh lab. They collaborated with Samuel Parry, the Franklin Payne Professor of Obstetrics and Gynecology; Christos Coutifaris, the Nancy and Richard Wolfson Professor of Obstetrics and Gynecology in Penn’s Perelman School of Medicine; and Emily Su, assistant professor of obstetrics and gynecology in the Anschutz Medical School of the University of Colorado Denver.

The researchers’ placenta-on-a-chip is a clear silicone device with two parallel microfluidic channels separated by a porous membrane. On one side of those pores, trophoblast cells, which are found at the placental interface with maternal blood, are grown. On the other side are endothelial cells, found on the interior of fetal blood vessels. The layers of those two cell types mimic the placental barrier, the gatekeeper between the maternal and fetal circulatory systems.

“That barrier,” Blundell said, “mediates all transport between mother and fetus during pregnancy. Nutrients, but also foreign agents like viruses, need to be either transported by that barrier or stopped.”

“One of the most important function of the placental barrier is transport,” Huh said, “so it’s essential for us to mimic that functionality.”

In 2013, Huh and his collaborators at Seoul National University conducted a preliminary study to create a microfluidic device for culturing trophoblast cells and fetal endothelial cells. This model, however, lacked the ability to form physiological placental tissue and accurately simulate transport function of the placental barrier.

In their new study, the Penn researchers have demonstrated that the two layers of cells continue to grow and develop while inside the chip, undergoing a process known as “syncytialization.”

“The placental cells change over the course of pregnancy,” Huh said. “During pregnancy, the placental trophoblast cells actually fuse with one another to form an interesting tissue called syncytium. The barrier also becomes thinner as the pregnancy progresses, and with our new model we’re able to reproduce this change.

“This process is very important because it affects placental transport and was a critical aspect not represented in our previous model.”

The Penn team validated the new model by showing glucose transfer rates across this syncytialized barrier matched those measured in perfusion studies of donated human placentae.

While useful in providing this type of baseline, donated placental tissue can be problematic for doing many of the types of studies necessary for fully understanding the structure and function of the placenta, especially as it pertains to diseases and disorders.

“The placenta is arguably the least understood organ in the human body,” Huh said, “and much remains to be learned about how transport between mother and fetus works at the tissue, cellular and molecular levels. An isolated whole organ is an not ideal platform for these types of mechanistic studies.”

“Beyond the scarcity of samples,” Blundell said, “there’s a limited lifespan of how long the tissue remains viable, for only a few hours after delivery, and the system that is used to perfuse the tissue and perform transport studies is complex.”

While the placenta-on-a-chip is still in the early stages of testing, researchers at Penn and beyond are already planning to use it in studies on preterm birth.

“This effort,” Parry said, “was part of the much larger Prematurity Research Center here at Penn, one of five centers around the country funded by the March of Dimes to study the causes of preterm birth. The rate of preterm birth is about 10 to 11 percent of all pregnancies. That rate has not been decreasing, and interventions to prevent preterm birth have been largely unsuccessful.”

As part of a $10 million grant from the March of Dimes that established the Center, Parry and his colleagues research metabolic changes that may be associated with preterm birth using in vitro placental cell lines and ex vivo placental tissue. The grant also supported their work with the Huh lab to develop new tools that could model preterm birth-associated placental dysfunction and inform such research efforts.

“Since publishing this paper,” Samuel Parry said, “we’ve reached out to the principal investigators at the other four March of Dimes sites and offered to provide them this model to use in their experiments.”

“Eventually,” Huh said, “we hope to leverage the unique capabilities of our model to demonstrate the potential of organ-on-a-chip technology as a new strategy to innovate basic and translational research in reproductive biology and medicine.”

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

A microphysiological model of the human placental barrier by Cassidy Blundell, Emily R. Tess, Ariana S. R. Schanzer, Christos Coutifaris, Emily J. Su, Samuel Parry. and Dongeun Huh. Lab Chip, 2016, Advance Article DOI: 10.1039/C6LC00259E First published online 20 May 2016

I believe this paper is behind a paywall.

One final note, I thought this was a really well written news release.

3D brain-on-a-chip from the University of Twente

Dutch researchers have developed a 3D brain-on-a-chip according to a June 23, 2016 news item on Nanowerk,

To study brain cell’s operation and test the effect of medication on individual cells, the conventional Petri dish with flat electrodes is not sufficient. For truly realistic studies, cells have to flourish within three-dimensional surroundings.

Bart Schurink, researcher at University of Twente’s MESA+ Institute for Nanotechnology, has developed a sieve with 900 openings, each of which has the shape of an inverted pyramid. On top of this array of pyramids, a micro-reactor takes care of cell growth. Schurink defends his PhD thesis June 23 [2016].

A June 23, 2016 University of Twente press release, which originated the news item, provides more detail,

A brain-on-a-chip demands more than a series of electrodes in 2D, on which brain cells can be cultured. To mimic the brain in a realistic way, you need facilities for fluid flow, and the cells need some freedom for themselves even when they are kept at predefined spaces. Schurink therefore developed a micro sieve structure with hundreds of openings on a 2 by 2 mm surface. Each of these holes has the shape of  an inverted pyramid. Each pyramid, in turn, is equipped with an electrode, for measuring electrical signals or sending stimuli to the network. At the same time, liquids can flow through tiny holes, needed to capture the cells and for sending nutrients or medication to a single cell.

NEURONAL NETWORK

After neurons have been placed inside all the pyramids, they will start to form a network. This is not just a 2D network between the holes: by placing a micro reactor on top of the sieve, a neuron network can develop in the vertical direction as well. Growth and electrical activity can be monitored subsequently: each individual cell can be identified by the pyramid it is in. Manufacturing this system, demands a lot of both the production facilities at UT’s NanoLab and of creative solutions the designers come up with. For example, finding the proper way of guaranteeing  the same dimensions for every hole, is quite challenging.

Schurink’s new µSEA (micro sieve electrode array) has been tested with living cells, from the brains of laboratory rats. Both the positioning of the cells and neuronal network growth have been tested. The result of this PhD research is a fully new research platform for performing research on the brain, diseases and effects of medication.

Schurink (1982) has conducted his research within the group Meso Scale Chemical Systems, of Prof Han Gardeniers. The group is part of the MESA+ Institute for Nanotechnology of the University of Twente. Schurink’s thesis is titled ‘Microfabrication and microfluidics for 3D brain-on-chip’ …

I have written about one other piece about a ‘3D’ organ-on-a-chip project in China (my Jan. 29, 2016 posting).

University of Toronto (Canada) researchers and lab-grown heart and liver tissue (person-on-a-chip)

Usually called ‘human-on-a-chip’, a team at the University of Toronto have developed a two-organ ‘person on a chip’ according to a March 7, 2016 news item on phys.org (Note: Links have been removed),

Researchers at U of T [University of Toronto] Engineering have developed a new way of growing realistic human tissues outside the body. Their “person-on-a-chip” technology, called AngioChip, is a powerful platform for discovering and testing new drugs, and could eventually be used to repair or replace damaged organs.

Professor Milica Radisic (IBBME, ChemE), graduate student Boyang Zhang and the rest of the team are among those research groups around the world racing to find ways to grow human tissues in the lab, under conditions that mimic a real person’s body. They have developed unique methods for manufacturing small, intricate scaffolds for individual cells to grow on. These artificial environments produce cells and tissues that resemble the real thing more closely than those grown lying flat in a petri dish.

The team’s recent creations have included BiowireTM—an innovative method of growing heart cells around a silk suture—as well as a scaffold for heart cells that snaps together like sheets of Velcro. But AngioChip takes tissue engineering to a whole new level. “It’s a fully three-dimensional structure complete with internal blood vessels,” says Radisic. “It behaves just like vasculature, and around it there is a lattice for other cells to attach and grow.” …

A March 7, 2016 University of Toronto news release (also on EurekAlert), which originated the news item, provides more detail about the AngioChip,

Zhang built the scaffold out of POMaC, a polymer that is both biodegradable and biocompatible. The scaffold is built out of a series of thin layers, stamped with a pattern of channels that are each about 50 to 100 micrometres wide. The layers, which resemble the computer microchips, are then stacked into a 3D structure of synthetic blood vessels. As each layer is added, UV light is used to cross-link the polymer and bond it to the layer below.

When the structure is finished, it is bathed in a liquid containing living cells. The cells quickly attach to the inside and outside of the channels and begin growing just as they would in the human body.

“Previously, people could only do this using devices that squish the cells between sheets of silicone and glass,” says Radisic. “You needed several pumps and vacuum lines to run just one chip. Our system runs in a normal cell culture dish, and there are no pumps; we use pressure heads to perfuse media through the vasculature. The wells are open, so you can easily access the tissue.”

Using the platform, the team has built model versions of both heart and liver tissues that function like the real thing. “Our liver actually produced urea and metabolized drugs,” says Radisic. They can connect the blood vessels of the two artificial organs, thereby modelling not just the organs themselves, but the interactions between them. They’ve even injected white blood cells into the vessels and watched as they squeezed through gaps in the vessel wall to reach the tissue on the other side, just as they do in the human body.

The news release also mentions potential markets and the work that needs to be accomplished before AngioChip is available for purchase,

AngioChip has great potential in the field of pharmaceutical testing. Current drug-testing methods, such as animal testing and controlled clinical trials, are costly and fraught with ethical concerns. Testing on lab-grown human tissues would provide a realistic model at a fraction of the cost, but this area of research is still in its infancy. “In the last few years, it has become possible to order cultures of human cells for testing, but they’re grown on a plate, a two-dimensional environment,” says Radisic. “They don’t capture all the functional hallmarks of a real heart muscle, for example.”

A more realistic platform like AngioChip could enable drug companies to detect dangerous side effects and interactions between organ compartments long before their products reach the market, saving countless lives. It could also be used to understand and validate the effectiveness of current drugs and even to screen libraries of chemical compounds to discover new drugs. Through TARA Biosystems Inc., a spin-off company co-founded by Radisic, the team is already working on commercializing the technology.

In future, Radisic envisions her lab-grown tissues being implanted into the body to repair organs damaged by disease. Because the cells used to seed the platform can come from anyone, the new tissues could be genetically identical to the intended host, reducing the risk of organ rejection. Even in its current form, the team has shown that the AngioChip can be implanted into a living animal, its artificial blood vessels connected to a real circulatory system. The polymer scaffolding itself simply biodegrades after several months.

The team still has much work to do. Each AngioChip is currently made by hand; if the platform is to be used industrially, the team will need to develop high-throughput manufacturing methods to create many copies at once. Still, the potential is obvious. “It really is multifunctional, and solves many problems in the tissue engineering space,” says Radisic. “It’s truly next-generation.”

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

Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis by Boyang Zhang, Miles Montgomery, M. Dean Chamberlain, Shinichiro Ogawa, Anastasia Korolj, Aric Pahnke, Laura A. Wells, Stéphane Massé, Jihye Kim, Lewis Reis, Abdul Momen, Sara S. Nunes, Aaron R. Wheeler, Kumaraswamy Nanthakumar, Gordon Keller, Michael V. Sefton, & Milica Radisic. Nature Materials (2016) doi:10.1038/nmat4570 Published online 07 March 2016

This paper is behind a paywall.

The researchers have made two images illustrating their work available. There’s this still image,

These tiny polymer scaffolds contain channels that are about 100 micrometres wide, about the same diameter as a human hair. When seeded with cells, the channels act as artificial blood vessels. By mimicking tissues in the human heart and other organs, these scaffolds provide a new way to test drugs for potentially dangerous side effects. (Image: Tyler Irving/Boyang Zhang/Kevin Soobrian)

These tiny polymer scaffolds contain channels that are about 100 micrometres wide, about the same diameter as a human hair. When seeded with cells, the channels act as artificial blood vessels. By mimicking tissues in the human heart and other organs, these scaffolds provide a new way to test drugs for potentially dangerous side effects. (Image: Tyler Irving/Boyang Zhang/Kevin Soobrian)

Perhaps more intriguing is this one,

UofT_AngioChipMoving

When seeded with heart cells, the flexible polymer scaffold contracts with a regular rhythm, just like real heart tissue. (Image: Boyang Zhang)

I have mentioned ‘human-on-a-chip’ projects many times here and as the news release writer notes, there is an international race. My July 1, 2015 posting (cross-posted from the June 30, 2015 posting [Testing times: the future of animal alternatives] on the International Innovation blog [a CORDIS-listed project dissemination partner for FP7 and H2020 projects]) notes a couple of those projects,

Organ-on-a-chip projects use stem cells to create human tissues that replicate the functions of human organs. Discussions about human-on-a-chip activities – a phrase used to describe 10 interlinked organ chips – were a highlight of the 9th World Congress on Alternatives to Animal Testing held in Prague, Czech Republic, last year. One project highlighted at the event was a joint US National Institutes of Health (NIH), US Food and Drug Administration (FDA) and US Defense Advanced Research Projects Agency (DARPA) project led by Dan Tagle that claimed it would develop functioning human-on-a-chip by 2017. However, he and his team were surprisingly close-mouthed and provided few details making it difficult to assess how close they are to achieving their goal.

By contrast, Uwe Marx – Leader of the ‘Multi-Organ-Chip’ programme in the Institute of Biotechnology at the Technical University of Berlin and Scientific Founder of TissUse, a human-on-a-chip start-up company – claims to have sold two-organ chips. He also claims to have successfully developed a four-organ chip and that he is on his way to building a human-on-a-chip. Though these chips remain to be seen, if they are, they will integrate microfluidics, cultured cells and materials patterned at the nanoscale to mimic various organs, and will allow chemical testing in an environment that somewhat mirrors a human.

As for where the University of Toronto efforts fit into the race, I don’t know for sure. It’s the first time I’ve come across a reference to liver tissue producing urea but I believe there’s at least one other team in China which has achieved a three-dimensional, more lifelike aspect for liver tissue in my Jan. 29, 2016 posting ‘Constructing a liver’.

North Carolina universities go beyond organ-on-a-chip

The researchers in the North Carolina universities involved in this project have high hopes according to an Oct. 9, 2015 news item on Nanowerk,

A team of researchers from the University of North Carolina at Chapel Hill and NC State University has received a $5.3 million, five-year Transformative Research (R01) Award from the National Institutes of Health (NIH) to create fully functioning versions of the human gut that fit on a chip the size of a dime.

Such “organs-on-a-chip” have become vital for biomedical research, as researchers seek alternatives to animal models for drug discovery and testing. The new grant will fund a technology that represents a major step forward for the field, overcoming limitations that have mired other efforts.

The technology will use primary cells derived directly from human biopsies, which are known to provide more relevant results than the immortalized cell lines used in current approaches. In addition, the device will sculpt these cells into the sophisticated architecture of the gut, rather than the disorganized ball of cells that are created in other miniature organ systems.

“We are building a device that goes far beyond the organ-on-a-chip,” said Nancy L. Allbritton, MD, PhD, professor and chair of the UNC-NC State joint department of biomedical engineering and one of four principle investigators on the NIH grant. “We call it a ‘simulacrum,’ [emphasis mine] a term used in science fiction to describe a duplicate. The idea is to create something that is indistinguishable from your own gut.”

I’ve come across the term ‘simulacrum’ in relation to philosophy so it’s a bit of a surprise to find it in a news release about an organ-on-a-chip where it seems to have been redefined somewhat. Here’s more from the Simulacrum entry on Wikipedia (Note: Links have been removed),

A simulacrum (plural: simulacra from Latin: simulacrum, which means “likeness, similarity”), is a representation or imitation of a person or thing.[1] The word was first recorded in the English language in the late 16th century, used to describe a representation, such as a statue or a painting, especially of a god. By the late 19th century, it had gathered a secondary association of inferiority: an image without the substance or qualities of the original.[2] Philosopher Fredric Jameson offers photorealism as an example of artistic simulacrum, where a painting is sometimes created by copying a photograph that is itself a copy of the real.[3] Other art forms that play with simulacra include trompe-l’œil,[4] pop art, Italian neorealism, and French New Wave.[3]

Philosophy

The simulacrum has long been of interest to philosophers. In his Sophist, Plato speaks of two kinds of image making. The first is a faithful reproduction, attempted to copy precisely the original. The second is intentionally distorted in order to make the copy appear correct to viewers. He gives the example of Greek statuary, which was crafted larger on the top than on the bottom so that viewers on the ground would see it correctly. If they could view it in scale, they would realize it was malformed. This example from the visual arts serves as a metaphor for the philosophical arts and the tendency of some philosophers to distort truth so that it appears accurate unless viewed from the proper angle.[5] Nietzsche addresses the concept of simulacrum (but does not use the term) in the Twilight of the Idols, suggesting that most philosophers, by ignoring the reliable input of their senses and resorting to the constructs of language and reason, arrive at a distorted copy of reality.[6]

Postmodernist French social theorist Jean Baudrillard argues that a simulacrum is not a copy of the real, but becomes truth in its own right: the hyperreal. Where Plato saw two types of representation—faithful and intentionally distorted (simulacrum)—Baudrillard sees four: (1) basic reflection of reality; (2) perversion of reality; (3) pretence of reality (where there is no model); and (4) simulacrum, which “bears no relation to any reality whatsoever”.[7] In Baudrillard’s concept, like Nietzsche’s, simulacra are perceived as negative, but another modern philosopher who addressed the topic, Gilles Deleuze, takes a different view, seeing simulacra as the avenue by which an accepted ideal or “privileged position” could be “challenged and overturned”.[8] Deleuze defines simulacra as “those systems in which different relates to different by means of difference itself. What is essential is that we find in these systems no prior identity, no internal resemblance”.[9]

Getting back to the proposed research, an Oct. (?), 2015 University of North Carolina news release, which originated the news item, describes the proposed work in more detail,

Allbritton is an expert at microfabrication and microengineering. Also on the team are intestinal stem cell expert Scott T. Magness, associate professor of medicine, biomedical engineering, and cell and molecular physiology in the UNC School of Medicine; microbiome expert Scott Bultman, associate professor of genetics in the UNC School of Medicine; and bioinformatics expert Shawn Gomez, associate professor of biomedical engineering in UNC’s College of Arts and Sciences and NC State.

The impetus for the “organ-on-chip” movement comes largely from the failings of the pharmaceutical industry. For just a single drug to go through the discovery, testing, and approval process can take as many as 15 years and as much as $5 billion dollars. Animal models are expensive to work with and often don’t respond to drugs and diseases the same way humans do. Human cells grown in flat sheets on Petri dishes are also a poor proxy. Three-dimensional “organoids” are an improvement, but these hollow balls are made of a mishmash of cells that doesn’t accurately mimic the structure and function of the real organ.

Basically, the human gut is a 30-foot long hollow tube made up of a continuous single-layer of specialized cells. Regenerative stem cells reside deep inside millions of small pits or “crypts” along the tube, and mature differentiated cells are linked to the pits and live further out toward the surface. The gut also contains trillions of microbes, which are estimated to outnumber human cells by ten to one. These diverse microbial communities – collectively known as the microbiota – process toxins and pharmaceuticals, stimulate immunity, and even release hormones to impact behavior.

To create a dime-sized version of this complex microenvironment, the UNC-NC State team borrowed fabrication technologies from the electronics and microfluidics world. The device is composed of a polymer base containing an array of imprinted or shaped “hydrogels,” a mesh of molecules that can absorb water like a sponge. These hydrogels are specifically engineered to provide the structural support and biochemical cues for growing cells from the gut. Plugged into the device will be various kinds of plumbing that bring in chemicals, fluids, and gases to provide cues that tell the cells how and where to differentiate and grow. For example, the researchers will engineer a steep oxygen gradient into the device that will enable oxygen-loving human cells and anaerobic microbes to coexist in close proximity.

“The underlying concept – to simply grow a piece of human tissue in a dish – doesn’t seem that groundbreaking,” said Magness. “We have been doing that for a long time with cancer cells, but those efforts do not replicate human physiology. Using native stem cells from the small intestine or colon, we can now develop gut tissue layers in a dish that contains stem cells and all the differentiated cells of the gut. That is the thing stem cell biologists and engineers have been shooting for, to make real tissue behave properly in a dish to create better models for drug screening and cell-based therapies. With this work, we made a big leap toward that goal.”

Right now, the team has a working prototype that can physically and chemically guide mouse intestinal stem cells into the appropriate structure and function of the gut. For several years, Magness has been isolating and banking human stem cells from samples from patients undergoing routine colonoscopies at UNC Hospitals.

As part of the grant, he will work with the rest of the team to apply these stem cells to the new device and create “simulacra” that are representative of each patient’s individual gut. The approach will enable researchers to explore in a personalized way how both the human and microbial cells of the gut behave during healthy and diseased states.

“Having a system like this will advance microbiota research tremendously,” said Bultman. “Right now microbiota studies involve taking samples, doing sequencing, and then compiling an inventory of all the microbes in the disease cases and healthy controls. These studies just draw associations, so it is difficult to glean cause and effect. This device will enable us to probe the microbiota, and gain a better understanding of whether changes in these microbial communities are the cause or the consequence of disease.”

I wish them good luck with their work and to end on another interesting note, the concept of organs-on-a-chip won a design award. From a June 22, 2015 article by Oliver Wainwright for the Guardian (Note: Links have been removed),

Meet the Lung-on-a-chip, a simulation of the biological processes inside the human lung, developed by the Wyss Institute for Biologically Inspired Engineering at Harvard University – and now crowned Design of the Year by London’s Design Museum.

Lined with living human cells, the “organs-on-chips” mimic the tissue structures and mechanical motions of human organs, promising to accelerate drug discovery, decrease development costs and potentially usher in a future of personalised medicine.

“This is the epitome of design innovation,” says Paola Antonelli, design curator at New York’s Museum of Modern Art [MOMA], who nominated the project for the award and recently acquired organs-on-chips for MoMA’s permanent collection. “Removing some of the pitfalls of human and animal testing means, theoretically, that drug trials could be conducted faster and their viable results disseminated more quickly.”

Whodathunkit? (Tor those unfamiliar with slang written in this form: Who would have thought it?)

Job posting (post doc in tissue engineering [organ-on-a-chip]) for the Istituto Italiano di Technologia

Here’s the posting (deadline is July 19, 2015),

Istituto Italiano di Tecnologia (IIT), Genova, Italy (http://www.iit.it) is a private law Foundation, created with special Government Law no. 269 dated September 30th 2003 with the objective of promoting Italy’s technological development and higher education in science and technology. Research at IIT is carried out in highly innovative scientific fields with state-of-the-art technology.

A post-doc position to develop “Organs-on-Chips” is available in the Laboratory of Nanotechnology for Precision Medicine at IIT.

Candidates should have a PhD in Tissue Engineering or closely related fields and an excellent publication record and should be highly motivated to work in an interdisciplinary team.

The candidate will work on the development of microfluidic-based organs-on-chips.

These microchips will be used to recapitulate the microarchitecture and functions of living organs and pathological tissues such as cancer and will possibly form an accurate alternative to traditional animal testing and enable high-throughput screening of drugs and nanomedicines.

The candidate should have:

  • strong skills in tissue engineering as well as in molecular, cellular and in vivo tumor biology;
  • documented experience in primary cell culture and analysis;
  • excellent oral and written communication skills in English and the ability to work both independently and as part of a multidisciplinary team.

Interested applicants should contact directly Dr. Paolo Decuzzi ( paolo.decuzzi@iit.it) for any informal queries.

For a formal application  please send CV, list of publications with Impact Factor and names and email addresses of 2 referees to applications@iit.it

Please apply by July 19, 2015 quoting “Post doc position in Tissue Engineering” in the mail subject. [emphasis mine]

In order to comply with Italian law (art. 23 of Privacy Law of the Italian Legislative Decree n. 196/03), the candidate is kindly asked to give his/her consent to allow Istituto Italiano di Tecnologia to process his/her personal data.

We inform you that the information you provide will be solely used for the purpose of evaluating and selecting candidates in order to meet the requirements of Istituto Italiano di Tecnologia.

Your data will be processed by Istituto Italiano di Tecnologia, with its headquarters in Genoa, Via Morego 30, acting as the Data Holder, using computer and paper-based means, observing the rules on the protection of personal data, including those relating to the security of data, and they will not be communicated to thirds.

Please also note that, pursuant to art.7 of Legislative Decree 196/2003, you may exercise your rights at any time as a party concerned by contacting the Data Holder.

Istituto Italiano di Tecnologia is an Equal Opportunity Employer that actively seeks diversity in the workforce.

Don’t forget when preparing your application, should you be living on the West Coast of Canada or the US (not sure about Mexico as its coast veers east somewhat), Italy is +9 hours . This means you’d best get your application submitted by 3 pm PST on July 19, 2015.

University of British Columbia (Canada) discovers the ‘organ-on-a-chip’ and plans to host a July 2014 workshop

My latest piece about an ‘organ-on-a-chip’ project was a July 26, 2012 posting titled Organ chips for DARPA (Defense Advanced Research Projects Agency) featuring the Wyss Institute (which pops up again in the latest news I have from the University of British Columbia [UBC; located in Vancouver, Canada)]). First, here’s more about that 2012 announcement,,

The Wyss Institute will receive up to  $37M US for a project that integrates ten different organ-on-a-chip projects into one system. From the July 24, 2012 news release on EurekAlert,

With this new DARPA funding, Institute researchers and a multidisciplinary team of collaborators seek to build 10 different human organs-on-chips, to link them together to more closely mimic whole body physiology, and to engineer an automated instrument that will control fluid flow and cell viability while permitting real-time analysis of complex biochemical functions. As an accurate alternative to traditional animal testing models that often fail to predict human responses, this instrumented “human-on-a-chip” will be used to rapidly assess responses to new drug candidates, providing critical information on their safety and efficacy.

This unique platform could help ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. As a result, the quality and quantity of new drugs moving successfully through the pipeline and into the clinic may be increased, regulatory decision-making could be better informed, and patient outcomes could be improved.

Jesse Goodman, FDA Chief Scientist and Deputy Commissioner for Science and Public Health, commented that the automated human-on-chip instrument being developed “has the potential to be a better model for determining human adverse responses. FDA looks forward to working with the Wyss Institute in its development of this model that may ultimately be used in therapeutic development.”

It’s nice to see that there’s interest in this area of research at UBC. From the Dec. 30, 2013 UBC news release by Gian-Paolo Mendoza which describes James Feng’s (professor in biological and chemical engineering) interest in the future possibilities offered by ‘organ-on-a-chip’ research,

“The potential is tremendous,” says Feng. “The main impact of organs grown this way will be on the design of drugs; the understanding of the pathological processes.”

Dr. Feng’s group carries out research in three broad areas: mechanics of biological cells and tissues, interfacial fluid dynamics, and mechanics and rheology of complex fluids.

The group has an inter-disciplinary flavour–crosscutting applied mathematics, cell biology, soft-matter physics and chemical and biomedical engineering—that is well-suited for exploring this burgeoning technology.

Feng cites a Harvard study [Ed. Note: This is the work being done at the Wyss Institute] using a small silicon device that holds a thin layer of real cell membranes capable of producing motion similar to the heaving and breathing of a lung.

Organ models designed this way have the potential to be more accurate in drug and treatment trials, says Feng, as they can better mimic the functions of human organs, as opposed to animal models which are the current research standard.

“It’s more controlled and you can simplify the process much faster,” said Feng.

“Harvard researchers also injected drugs into their chip model to see how it changed its behaviour and to see the tissue’s reaction to mechanical or chemical disturbance,” he added.

“It’s very important for drug design and discovery and the pharmaceutical industry would be tremendously interested in that.”

In addition, organs on a chip present a less controversial option for organ model testing compared to stem cell research. According to Feng, this is because their ultimate goals are very different from each other.

“The research that tried to grow organs directly from stem cells is aiming for eventually implantable organs,” he said. “The idea of making the chip is to work toward replacing animal models, so as to be more accurate and realistic like human organs. While the ability to replicate a complex human organ function remains far off, the direction appeals to anyone who is hoping to reduce the use of animals in research.”

Here’s the ‘lung-on-a-chip’ video the Wyss Institute has produced,

By contrast with ‘organ-on-a-chip’, the ‘lab-on-a-chip’ does not simulate the action of organs responding to various experimental therapeutic measures but makes standard testing and diagnostic procedures, such as blood tests, much faster, cheaper, and, in some cases, much less invasive as per my February 15, 2011 posting  which included some information about a local (Vancouver, Canada) project, the PROOF.(Prevention of Organ Failure) Centre.

The ‘organ-on-a-chip’ will help make clinical trials easier and faster according to Feng (from the news release),

Feng says this kind of organ testing offers the possibility of greatly reducing cost and time required for clinical trials.

“By using computer simulations we can generate results and insights, and run virtual tests much more easily and quickly,” he says.

“We can test maybe hundreds or thousands of designs of organ chips to be able to tell you whether you should try those ten designs instead of the hundreds one by one.”

Feng, who has a background in aerospace engineering, says this new bio-technology has the potential to transform the development of artificial organs and drugs the way computer simulations have replaced the use of wind tunnels for designing aircrafts.

“That used to be the dominant mode of designing crafts,” he said, “but that’s being replaced by online computer simulations because we understand the principles of aerodynamics so well.”

There’s also recognition that UBC is a little late to the ‘party’,

While UBC’s efforts in the field are in the early stages, Feng is reaching out to researchers from other backgrounds. He will be inviting leading scientists to UBC in July 2014 for a workshop that will centre on the growth of artificial organs and computer simulations. He is also exploring ideas of his own.

“I have a collaboration with an engineering colleague on how to use the microfluidic chip, the technology used to emulate the lung in the Harvard study, as a way of measuring malaria-infected red cells,” he said, suggesting that this is just one of the countless ways this new technology could be used to fuel future innovation.

And since it’s Friday (Jan. 3, 2014), I thought it was time for a music video, and Pink’s ‘Let’s get the party started’ seems to fit the bill,,

Have a good first weekend of the year 2014!

Organ chips for DARPA (Defense Advanced Research Projects Agency)

The Wyss Institute will receive up to  $37M US for a project that integrates ten different organ-on-a-chip projects into one system. From the July 24, 2012 news release on EurekAlert,

With this new DARPA funding, Institute researchers and a multidisciplinary team of collaborators seek to build 10 different human organs-on-chips, to link them together to more closely mimic whole body physiology, and to engineer an automated instrument that will control fluid flow and cell viability while permitting real-time analysis of complex biochemical functions. As an accurate alternative to traditional animal testing models that often fail to predict human responses, this instrumented “human-on-a-chip” will be used to rapidly assess responses to new drug candidates, providing critical information on their safety and efficacy.

This unique platform could help ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. As a result, the quality and quantity of new drugs moving successfully through the pipeline and into the clinic may be increased, regulatory decision-making could be better informed, and patient outcomes could be improved.

Jesse Goodman, FDA Chief Scientist and Deputy Commissioner for Science and Public Health, commented that the automated human-on-chip instrument being developed “has the potential to be a better model for determining human adverse responses. FDA looks forward to working with the Wyss Institute in its development of this model that may ultimately be used in therapeutic development.”

Wyss Founding Director, Donald Ingber, M.D., Ph.D., and Wyss Core Faculty member, Kevin Kit Parker, Ph.D., will co-lead this five-year project.

I note that Kevin Kit Parker was mentioned in an earlier posting today (July 26, 2012) titled, Medusa, jellyfish, and tissue engineering, and Donald Ingber in my Dec.1e, 2011 posting about Shrilk and insect skeletons.

As for the Wyss Institute, here’s a description from the news release,

The Wyss Institute for Biologically Inspired Engineering at Harvard University (http://wyss.harvard.edu) uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, , Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature’s principles for self-organizing and self-regulating, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.

I hadn’t thought of an organ-on-a-chip as particularly bioinspired so I’ll have to think about that one for a while.