Tag Archives: lab-on-a-chip

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

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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!

Needles not needed for blood tests with implantable lab-on-a-chip

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Swiss Nano-Tera program researchers have developed an implantable lab-on-a-chip which can test blood and convey the results to your doctor (once they take the device out of the laboratory) according to a Mar. 19, 2013 news release on EurekAlert,

Humans are veritable chemical factories – we manufacture thousands of substances and transport them, via our blood, throughout our bodies. Some of these substances can be used as indicators of our health status. A team of EPFL (École Polytechnique Fédérale de Lausanne) scientists has developed a tiny device that can analyze the concentration of these substances in the blood. Implanted just beneath the skin, it can detect up to five proteins and organic acids simultaneously, and then transmit the results directly to a doctor’s computer. This method will allow a much more personalized level of care than traditional blood tests can provide. Health care providers will be better able to monitor patients, particularly those with chronic illness or those undergoing chemotherapy. The prototype, still in the experimental stages, has demonstrated that it can reliably detect several commonly traced substances. The research results will be published and presented March 20, 2013 in Europe’s largest electronics conference, DATE 13.

Design,  Automation, and Test in Europe (DATE) 2013 can be found here. For those of us who won’t be at the DATE 13 conference, this EPFL video highlights some of the research being presented there,

The EPFL Mar. 20, 2013 news release provides more information about the technology and potential applications,

The device was developed by a team led by EPFL scientists Giovanni de Micheli and Sandro Carrara. The implant, a real gem of concentrated technology, is only a few cubic millimeters in volume but includes five sensors, a radio transmitter and a power delivery system. Outside the body, a battery patch provides 1/10 watt of power, through the patient’s skin – thus there’s no need to operate every time the battery needs changing.

Information is routed through a series of stages, from the patient’s body to the doctor’s computer screen. The implant emits radio waves over a safe frequency. The patch collects the data and transmits them via Bluetooth to a mobile phone, which then sends them to the doctor over the cellular network.

…

Great care was taken in developing the sensors. To capture the targeted substance in the body – such as lactate, glucose, or ATP – each sensor’s surface is covered with an enzyme. “Potentially, we could detect just about anything,” explains De Micheli. “But the enzymes have a limited lifespan, and we have to design them to last as long as possible.” The enzymes currently being tested are good for about a month and a half; that’s already long enough for many applications. “In addition, it’s very easy to remove and replace the implant, since it’s so small.”

The electronics were a considerable challenge as well. “It was not easy to get a system like this to work on just a tenth of a watt,” de Micheli explains. The researchers also struggled to design the minuscule electrical coil that receives the power from the patch.

…

The implant could be particularly useful in chemotherapy applications. Currently, oncologists use occasional blood tests to evaluate their patients’ tolerance to a particular treatment dosage. In these conditions, it is very difficult to administer the optimal dose. …

In patients with chronic illness, the implants could send alerts even before symptoms emerge, and anticipate the need for medication. “In a general sense, our system has enormous potential in cases where the evolution of a pathology needs to be monitored or the tolerance to a treatment tested.”

The prototype has already been tested in the laboratory for five different substances, and proved as reliable as traditional analysis methods. The project brought together eletronics experts, computer scientists, doctors and biologists from EPFL, the Istituto di Ricerca di Bellinzona, EMPA (Swiss Federal Laboratories for Materials Science and Technology) and ETHZ (Eidgenössische Technische Hochschule Zürich). It is part of the Swiss Nano-Tera program, whose goal is to encourage interdisciplinary research in the environmental and medical fields. Researchers hope the system will be commercially available within 4 years. [emphases mine]

“Making this technology commercially available within four years” seems rather optimistic since the news release mentions laboratory testing only. Optimistic that is, unless the researchers are already running human clinical trials not mentioned in the news release.

One last thought, objects implanted into the body tend to break down over time as per hip and knee replacements. I wonder if this lab-on-a-chip could be subject to some of the same drawbacks.

Namdiatream; a European multimodal diagnostics project

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I’ve written about lab-on-a-chip projects, point-of-care diagnostics, and other such initiatives on several occasions, most recently in a Mar. 1, 2013 posting about a technique where powder is used to make the diagnostic device more portable. This time it was a Europe-wide project described in a Mar. 4, 2013 news item on Nanowerk,which caught my attention (Note: A link has been removed),

The plan of the EU-funded consortium Nanotechnological toolkits for multi-modal disease diagnostics and treatment monitoring (Namdiatream) is not to cure cancer, per se, but to boost the sensitivity of diagnostics and the ability to monitor progress during treatment. They focused on three types – breast, prostate and lung cancer.

… The prototype devices being developed during the four-year project will detect common cancer cells much earlier and, with timely treatment, improve the chances of recovery.

According to the project leader, Professor Yuri Volkov of Trinity College Dublin’s School of Medicine, the portable nanodevices are based on innovative lab-on-a-chip, -bead and -wire technologies applicable in different settings – clinical, research, or point of care (i.e. hospitals). These lab-on-x technologies exploit the photo-luminescent (‘glow-in-the-dark’ light emitting), plasmonic (‘light-on-a-wire’), magnetic and unique optical properties of nanomaterials.

Volkov offers some insight into how the project started and its current state of evolution (from the news item),

This is ground-breaking work made possible thanks to advanced technology but also to EU funding for cross-border investigations. Teams across Europe were doing related but fragmented research, suggests Prof. Volkov. This risked leaving a team dangling if their approach failed or lacked funding.

“So we integrated our research and identified joint strengths to help one another develop the best technological approaches in case something didn’t work in one, or synergies were identified, thereby increasing the chances of wider success.”

At its half-way stage, notes Prof. Volkov, Namdiatream underwent a natural evolution when it became clear that by merging and refocusing work in some areas – i.e. in fluorescent nanomaterial technology and magnetic nanowire barcodes – it would speed up industrial implementation efforts.

“Now, work on the preclinical prototype devices is well under way,” he confirms. But one of the many remaining challenges is to calibrate their sensitivity, so that they do not give false readings, for instance.

The Namdiatream (Nanotechnological Toolkits for Multi-Modal Disease Diagnostics and Treatment Monitoring) home page offers more detail about the project,

Namdiatream is a truly interdisciplinary and Pan-european consortium that builds around 7 High-Tech SMEs [small to medium enterprises], 2 Multinational industries and 13 academic institutions. NAMDIATREAM will develop nanotechnology-based toolkit to enable early detection and imaging of molecular biomarkers of the most common cancer types and of cancer metastases, as well as permitting the identification of cells indicative of early-stage disease onset. The project is built on the innovative technology concepts of super-sensitive “lab-on-a-bead”, “lab-on-a-chip” and “lab-on-a-wire” nano-devices.

Interestingly, this too was on the home page,

The ETP Nanomedicine documents point out that nanotechnology has yet to deliver practical solutions for the patients and clinicians in their struggle against common, socially and economically important diseases such as cancer. Therefore NAMDIATREAM results will firstly aim to deliver to the diagnostic and medical imaging device companies involved in the consortium, and the clinical and academic partners. This could further provide the basis for cancer therapeutics as it will be possible to accurately assess the kinetics of cancer cell destruction during the course of appropriate therapy.

Organ chips for DARPA (Defense Advanced Research Projects Agency)

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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.

More bimetallic nanoparticles

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Two days ago, I noted that I’d never encountered bimetallic nanoparticles before reading about the ‘Christmas decorations’ created by a Mexico/US research team (my Dec. 6, 2010 posting). Live and learn. Here’s another bimetallic (gold and silver this time too) news item on Nanowerk,

Shrink Nanotechnologies, Inc. (“Shrink”), an innovative nanotechnology company developing products and licensing opportunities in the solar energy industry, medical diagnostics and sensors and biotechnology research and development tools businesses, announced today that Shrink’s MetalFluor™ technology was studied, reported on and made the front cover of the November issue of Applied Physics Letters (“Bimetallic nanopetals for thousand-fold fluorescence enhancements”). [the article is behind a paywall]

I was most interested to note that at least one of the authors is a researcher associated with the company that issued the news release trumpeting the article in Applied Physics Letters. From the news item on Nanowerk,

The Company’s technology and the work being performed by Dr. Michelle Khine, our scientific founder, continues to gain high praise from leading academic journals. [emphases mine] The studies relate to potential commercial applications of this technology. Of note, the article states, “Because we have a range of nanostructure and nanogap sizes, we can ensure that we can achieve huge fluorescent enhancements on our substrate. These advantages show great potential for low-cost biomedical sensing at single molecular levels at physiological concentrations.” The Company believes that this article is further evidence that certain medical diagnostics tests, a multi-billion dollar annual industry in the United States alone, can provide physicians, patients and other medical professionals with better results using lower quantities of specimens using MetalFluor™ technologies.

Here’s more about possible uses for the technology cited in the article in Applied Physics Letters (citation: Bimetallic nanopetals for thousand-fold fluorescence enhancements by Chi-Cheng Fu1, Giulia Ossato, Maureen Long, Michelle A. Digman, Ajay Gopinathan, Luke P. Lee, Enrico Gratton, and Michelle Khine in vol. 97, issue no. 20, Nov. 15, 2010),

Our method can be easily integrated with microfluidic devices to combine with high throughput lab-on-chip techniques. Importantly, because of–not in spite of–the “variability” in our substrate, we do not need to choose an esoteric dye such that it would match our plasmon resonance. Because we have a range of nanostructure and nanogap sizes, we can ensure that we can achieve huge fluorescence enhancements on our substrate. These advantages show great potential for low-cost biomedical sensing at single molecular levels at physiological concentrations.

The company Khine founded is very interesting from an organizational perspective (the news item on Nanowerk),

Shrink is a first of its kind FIGA™ organization. FIGA companies bring together diverse contributions from leaders in the worlds of finance, industry, government and academia. [emphases mine] Shrink’s solutions, including its diverse polymer substrates, nano-devices and biotech research tools, among others, are designed to be ultra-functional and mechanically superior in the solar energy, environmental detection, stem cell and biotechnology markets. The Company’s products are based on a pre-stressed plastic called NanoShrink™, and on a patent-pending manufacturing process called the ShrinkChip Manufacturing Solution™. Shrink’s unique materials and manufacturing solution represents a new paradigm in the rapid design, low-cost fabrication and manufacture of nano-scale devices for numerous significant markets.

I can’t make much of this academic/business hybrid but I am intrigued and will watch its progress with some interest. You can visit the Shrink Nanotechnologies website here.

Simon Fraser University uses gold nanoparticles for anti-folding

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It always amazes me when something pops in my email and turns out to be related to one of my latest postings. Today, Simon Fraser University sent me a news release about Paul Li and his lab-on-a-chip work where he’s trying to keep DNA strands separate. From the news release,

A Simon Fraser University chemist who pioneered lab-on-a-biochip technology six years ago has struck gold in the research world again, this time literally.

Paul Li has combined nanoscale-sized-particles of gold with two powerful tools in molecular biology to make DNA analysis more than 10 times faster at room temperature, rather than previously required higher temperatures.

Li has sped up gene identification by fusing the slide-like microarray’s ability to identify known DNA gene sequences with the multi-channel microfluidic device’s ability to quickly analyse small amounts of liquid.

The palm-sized hybrid biochip is roughly the same thickness as the Canadian Loonie.

But what really makes the invention a biomedical gold mine is the addition of gold nanoparticles to the liquid being analysed on it. Mixed with DNA, tiny spheres of gold act as mini magnets that adhere to each of the DNA’s twin strands.

When the DNA is heated, the two strands separate. The gold nanoparticles keep them apart, which enables scientists to probe each strand with other pieces of DNA that are engineered to recognize known gene sequences.

“The key benefit of the gold is that it allows us to do our analysis at room temperature (25 degrees C),” explains Li. “That is half the conventional temperature needed, which requires the use of an apparatus that tolerates high temperatures.

“More importantly, DNA sequences with slight differences are now differentiated by the nanoparticle, but not by the high temperature.”

This invention will revolutionize researchers’ ability to probe biological samples and detect genes for forensic analysis, disease detection and drug development.

I may have stretched this just a bit by calling anti-folding but this process which uses the gold nanoparticles to keep the DNA strands from adhering to each other contrasts with the work mentioned in today’s earlier post, Folding, origami, and shapeshifting and an article with over 50,000 authors, where DNA was used to keep ensure that carbon nanotubes don’t adhere to each other.