The end of animal testing? Human-organs-on-chips

They may look like humble little blocks, but these miracle devices could end animal testing, revolutionize the development of new drugs and lead us into a world of entirely personalized medicine.

Tiny tubes emerge from a small transparent block, pumping imperceptible amounts of fluid and air to and fro. It looks like a Fox’s Glacier Mint has been plugged into a life support machine, but this humble chunk of see-through silicone is a model organ that could revolutionise the pharmaceutical industry, reducing the need for animal testing and speeding up the development of new drugs.

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 personalized medicine.

The micro-devices work by recreating the tissue interfaces of human organs inside a transparent polymer “chip”, so the behaviours of bacteria, drugs and human white blood cells can be easily monitored through a microscope. A tiny channel runs through the middle, divided along its length by a porous membrane, with human lung cells on one side and blood capillary cells on the other. By running air through one side and a blood-like solution through the other, while applying a flexing and stretching motion using a vacuum, the chip can simulate the processes of breathing.

“The organs-on-chips allow us to see biological mechanisms and behaviors that no one knew existed before,” says Don Ingber, founding director of the Wyss Institute. “We now have a window on the molecular-scale activities going on in human organs, including things that happen in human cells that don’t occur in animals. Most drug companies get completely different results in dogs, cats, mice and humans, but now they will be able to test the specific effects of drugs with greater accuracy and speed.”

Ingber and his team have developed a number of different organs-on-chips to date, including a kidney, liver and peristaltic gut-on-a-chip, while skin-on-a-chip is currently in development for the cosmetics industry and for testing household cleaning products.

The different organs can also be joined up in a network, allowing the journey of a drug to be followed through a simulated human body. The effects of an aerosol drug, of the kind dispensed by an asthma inhaler for example, can be observed in terms of how it enters the lungs, how it affects the heart, how it is metabolized by the liver and how it is excreted by the kidneys, with any adverse side-effects monitored along the way in real time. Four organs have already been tested together for a two-week trial period and in two years’ time, Ingber says they will have 10 organs up and running for a month-long test. So what next? Does this work lead the way to building an artificial human-on-a-chip?

Organ On Chips is Design of the Year

Paola Antonelli, the senior curator of design and architecture at the Museum of Modern Art, added an intriguing object to the museum’s permanent collection. It was a clear plastic chip, no bigger than a thumb drive, and it could soon change the way scientists develop and test life-saving medicines.

Called Organs-On-Chips, it’s exactly what it sounds like: A microchip embedded with hollow microfluidic tubes that are lined with human cells, through which air, nutrients, blood and infection-causing bacteria could be pumped. These chips get manufactured the same way companies like Intel make the brains of a computer. But instead of moving electrons through silicon, these chips push minute quantities of chemicals past cells from lungs, intestines, livers, kidneys and hearts. Networks of almost unimaginably tiny tubes give the technology its name microfluidicsand let the chips mimic the structure and function of complete organs, making them an excellent testbed for pharmaceuticals. The ultimate goal is to lessen dependence on animal test subjects and decrease time and cost for developing drugs. Last year, researchers from Harvard’s Wyss Institute for Biologically Inspired Engineering started a company called Emulate, which is now working with companies like Johnson & Johnson on just this idea: pre-clinical trial testing. The company is currently working on incorporating Emulate’s chips into its research and development programs.

When the Harvard team first published its findings on the chips in 2010, the research was purely scientific. Now, five years later, it’s not only been inducted into the world’s foremost design collection, it’s also been named Design of the Year.

Every year, London’s Design Museum names one project as the year’s best. Past winners have included Zaha Hadid’s ethically-questionable (but stunning) Heydar Aliyev Cultural Centre in Azerbaijan, a lightbulb, and a government website. That a piece of medical equipment developed by biological engineers is this year’s winner isn’t just a nod to the design’s worthiness. It also says something about how views of what counts as “design” are changing.

To be sure, Organs-On-Chips is aesthetically brilliant. Antonelli, who recently called synthetic biology the most exciting frontier in design, described the chips as the epitome of design innovation. “In some lucky cases, the form is striking,” she says, referring to objects born out of scientific research. “In this particular case, added bonus, not only is the form striking, but so is the function—the idea behind the object.” Like a biological system, the chip’s form dictates its function, and its form is undeniably beautiful. But that’s not the end of the story. “Most people say form follows function, but it’s exactly the opposite in biology,” says Donald Ingber, a bioengineer and founding director of the Wyss Institute, which developed the chip and is working on commercializing it. “Actually, that’s not fair. It’s a dynamic relationship.” The structure of a biological system will inevitably affect the way it works, but Ingber says the design principle works both ways. “If you change the function, you can actually modulate the structure,” he says, noting how the diameter of blood vessels will adapt to decrease the tension in people who develop hypertension.

Working on the microscale requires precision. The chip effectively replaces the three-dimensional structures of an organ the renal tubules of a kidney, the alveoli of the lungs, the veins in a liver—with tissue-lined microfluidic channels. Then it emulates the mechanics of those structures. For example, running air through a channel while using a vacuum to introduce a flexing motion will simulate the patterns of human breathing. The chip’s translucent polymer, in which the channels are encased, allows scientists to see what’s happening inside organs on the microscale. The prototypes can also be linked together to form a whole-body network of organs.

Organs-On-Chips embraces the most basic of design principles: efficiency. “Design in its greatest simplicity is minimizing any system down to its elements so as to have the greatest impact,” says Ingber. Like an increasing number of researchers, he understands that good science requires an understanding of good design. The principles that govern the two fields aren’t totally separate—in fact, design is a thread that runs through every field. It’s heartening when a big award reminds us of that.

Organ on Chips Can Revolutionalize Drug Testing

It takes up to 15 years and $5 billion for a new drug to make it through testing and earn approval from the U.S. Food and Drug Administration (FDA). Before researchers try a compound on humans, it’s tested at labs in petri dishes and on animals, such as mice and monkeys. More often than not, these studies produce mixed data that don’t tell researchers much about whether it is safe and effective for humans. For some time, scientists have been searching for ways to cut down on the cost and failure rate of drug testing. Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a beautiful solution: Organs-On-Chips.The clear and flexible polymer microchips are lined with human cells. Each one represents a different human organ system, such as lungs, heart and intestines. The institute’s goal is to create 10 different organ systems that can be joined together by blood vessel channels to simulate human physiology on a microscale and provide a cheaper, more reliable way to test new drugs.

The sophisticated architecture of these organs-on-chip which are about the size of a thumb drive has also earned the Wyss Institute recognition in the art world with a Design of the Year award from the Design Museum and placement in the Museum of Modern Art’s permanent collection.“The real power of this approach is that you have a window to the inner workings of life,” says Don Ingber, founding director of the Wyss Institute and a professor of Vascular Biology and of Bioengineering at Harvard University. “Anything you can ask at the molecular level, we could do in our chips.”In 2008, the team built and tested its first “organoid” chip to mimic the mechanical function of human lungs. It contains tiny channels separated by a porous membrane to create two distinct, hollow passageways—one lined with human lung cells and the other with capillary blood vessel cells. Air is suctioned through the side channels to emulate breathing. Ingber and his team introduced bacteria into the chip’s lung channel and white blood cells into the capillary channel. They observed that the white blood cells permeated the membrane and attacked the bacteria in the lung cell channel—exactly what would happen in human lungs fighting off an infection.In another experiment, the team at Wyss filled a chip’s lung cell channel with interleukin 2, a chemotherapy drug known to cause pulmonary edema, an accumulation of fluid in the lungs. When air entered the lung cell channel, the channel filled with fluid and then blood clots exactly what happens in the lungs of patients who develop this life-threatening condition. This proved the chips could provide real world information to scientists studying the effects of new drug compounds.The project has received support from the National Institutes of Health and the FDA. The Defense Advanced Research Projects Agency also recently awarded the institute a $37 million grant to create chips representing nearly all systems in the body. Ingber says some scientists are interested in using the chips to conduct research that would be unethical if performed on people, such as studying the effects of gamma radiation on the human body.Of course, the chips have limitations. “We can’t mimic consciousness; we can’t mimic compression on a joint,” says Ingber.Danilo Tagle, associate director for special initiatives at the National Center for Advancing Translational Sciences, a division of the NIH, is spearheading a similar organ-on-chip project. He suspects that in the beginning the chips will be used to “complement and supplement” animal studies, but will eventually become routine practice. The chips will also provide researchers with information on dosing at a much earlier stage in drug studies—particularly helpful because animals metabolize chemical substances at a different rate than humans. “You can go forward with a candidate drug with greater assurance and confidence that it will have the desired effect on humans,” says Tagle. “Biology is very complex.”

Incorporating the chips into drug testing could save millions of dollars and years of time on research. Some companies are already trying out the concept. Janssen Pharmaceuticals Company, a subsidiary of Johnson & Johnson, is using a version of the chips to understand how blood clots in the lungs. The information is essential to reduce the risk for this side effect of oncology drugs. Though there still aren’t enough data to prove the chips are reliable enough to put rodents out of a job, Ingber says it’s only a matter of time; they hope to have them tested and ready for market in two years. “The FDA has been very supportive,” he says. “They’ve told us if they are as good as animals that they would consider accepting data provided by a drug company from one of these models rather than an animal model.

The Evolve of Microfluidic Organ on Chips

Today almost everything is possible with the use of the technology everything around us can be easier. Technology such made a big difference in world as the time passes by especially in the medical world. One of the latest and hottest development in the world of medicines is the birth of organ on chips. An organ on chip is a microfluidic cell culture device created with microchip manufacturing methods that contains continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology. By recapitulating the multicellular architectures, tissue-tissue interfaces, physicochemical microenvironments and vascular perfusion of the body, these devices produce levels of tissue and organ functionality not possible with conventional 2D or 3D culture systems. They also enable high-resolution, real-time imaging and in vitro analysis of biochemical, genetic and metabolic activities of living cells in a functional tissue and organ context. This technology has great potential to advance the study of tissue development, organ physiology and disease etiology. In the context of drug discovery and development, it should be especially valuable for the study of molecular mechanisms of action, prioritization of lead candidates, toxicity testing and biomarker identification.

Some of the business company that makes it accessible to found the right chips that you are using in the labs is Corsolutions they are based in New York that truly embodies the users needs. Body-on-a-Chip is an emerging research area that cultures human organ tissue in microdevices to accurately mimic their structure and function. The goal is to develop the best predictive model of human response to therapies, drugs, cosmetics and other chemical compounds. The applications for Body-on-a-Chip are far-reaching.

Organ-on-chips could be the end of Animal Testing

The end of animal testing could finally be near as new smart microchips developed by engineers at the Harvard University promises to render the practice unnecessary. The new technology, aptly called organs-on-chip, is designed to simulate several human organ functions but on a microscale. These microchips can mimic the lungs, the intestines or the heart, making them ideal for testing cosmetics and drugs without using animal subjects and at lesser costs.

The revolutionary concept behind the Human Organs-On-Chip project was awarded the Design of the Year given by the London's Design Museum. It was able to beat out the self-driving car design developed by Google.

"The microdevices have the potential ability to deliver transformative change to pharmaceutical development and human healthcare due to the accuracy at which they emulate human organ-level functions," the developers of the organs-on-chips said.

"They stand to significantly reduce the need for animal testing by providing a faster, less expensive, less controversial and accurate means to predict whether new drug compounds will be successful in human clinical trials."

To create the microchips, the developers first had to produce a small plastic block with microchannels coursing through it. They then lined these tubes using a porous membrane with human cells taken from the lungs and several blood vessels.

This membrane layer is used to separate a solution of white blood cells required to kill off body infections from a space where cells of bacteria are kept.

The membranes are then expanded and contracted in order to allow the white blood cells to reach the bacteria cells and attack them, much like how they destroy infections in the body. Scientists would then be able to use the microchips to test the reaction of this immune system to various infectious diseases.

The design for the organs-on-chips was first conceptualized by Donald Ingber, founder of Harvard's Wyss Institute, and Dan Dongeun Huh, a former Wyss Institute developer, back in 2010.

"This is a big win towards achieving our Institute's mission of transforming medicine and the environment by developing breakthrough technologies and facilitating their translation from the benchtop to the marketplace," Ingber said.

Microfluidics Chips How It is Made

Microfluidic chips are the devices used in microfluidics in which a micro-channels network has been molded or patterned. Thanks to a various number of inlet and outlet ports, these microfluidic instruments allow your fluids to pass through different channels of different diameter, usually ranging from 5 to 500 μm1. The micro-channels network must be specifically designed for your application and the analyses you want to carry out (cell culture, organ-on-a-chip, DNA analysis etc.)

Microfluidic devices such as chips have many advantages as they can decrease your sample and reagent consumption and increase automation, thus minimizing your analysis time2. Such devices allow applications in many areas such as medicine, biology, chemistry and physics3. Three types of materials are commonly used to create microfluidic chips : silicon, glass, and polymers. Each material has its specific chemical and physical characteristics. The choice of the material depends on the needs and conditions of your applications (type of solvant, samples, etc.), the design of the chip you want to obtain and your budget.

For some experiments, a combination of these three materials will be needed to create the desired microfluidic chip:

MICROFLUIDIC CHIPS IN SILICON

Advantages of silicon are its superior thermal conductivity, surface stability and solvent compatibility. However no applications in optical detection can be done due to its optical opacity2, 4.

MICROFLUIDIC CHIPS IN GLASS Glass shares with silicon the same advantages mentioned above. Its well-defined surface chemistries, superior optical transparency and excellent high-pressure resistance2,4 make it a material of choice for many applications. Glass is also biocompatible, chemically inert, hydrophilic and allows efficient coatings. The main hurdle with this material remains its rather high cost, even though prices have been significantly reduced.

MICROFLUIDIC CHIPS IN POLYMERS Polymers offer an attractive alternative to glass and silicon as they are cheaper, robust and require faster fabrication processes4. Many polymers can be used to build chips : Polystyrene (PS), Polycarbonate (PC), Polyvinyl chloride (PVC), Cyclic Olefin Copolymer (COC), Polymethyl methacrylate (PMMA) and Polydimethylsiloxane (PDMS).

PDMS is the material of choice for fast prototyping microfluidic devices. PDMS chips are commonly used in laboratories, especially in the academic community due to their low cost and ease of fabrication. Here are listed main advantages of such chips: Oxygen and gas permeability Optical transparency, robustness Non toxicity Biocompatibility

One of the main drawbacks of PDMS chips is its hydrophobicity. Consequently, introducing aqueous solutions into the microchannels is difficult and hydrophobic analytes can adsorb onto the PDMS surface, thus interfering with analysis. There are now PDMS surface modification methods such as gas phase processing methods and wet chemical methods (or combination of both) to avoid issues due to hydrophobicity2. Another main issue of PDMS chips is that they are non-suitable for high pressure operation as it can alter channels geometry4.

Let Us Know More About Flow Meters

Flow meters is a device used to measure the flow rate or quantity of a gas or liquid moving through a pipe. Flow measurement applications are very diverse and each situation has its own constraints and engineering requirements. Flow meters are referred to by many names, such as flow gauge, flow indicator, liquid meter, etc. depending on the particular industry; however the function, to measure flow, remains the same.

Why do I need a precision flow meter? You might not! Precision flow meters are used to provide accurate monitoring and/or flow control. Some industrial applications require precise calculation of quantity.

What type of flow meter is best? There are no “universal” flow meters which are suitable for all applications. Selecting the proper technology for your application requires writing a flow specification which covers the use of the meter. There are usually trade-offs with each meter type, so knowing the critical specifications will be important. Things you must know:

What Gas or Liquid will be measured? Minimum and maximum flow rates. What are the accuracy requirements? The fluid temperature and viscosity. Fluid compatibility with the materials of construction (See our materials compatibility guide) The maximum pressure at the location. What pressure drop is allowable? Will the meter be mounted in a hazardous location? Is the fluid flow continuous or intermittent?