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Power in a small package: Organ-on-a-Chip

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Power in a small package: Organ-on-a-Chip is a new weapon in the fight for food-safety

By: Ryan Robinson, PhD

In the 20th and 21st century miniaturization and digitization are two factors that have dramatically improved both the quality and quantity of life in the developed world. Today, the device you carry in your pocket is likely to be several orders-of-magnitude more sophisticated and powerful than the billion-dollar multi-room computer system that helped to first put a man on the moon. The various merits of a digital society can be debated, but when you get down to brass-tacks we are undoubtedly healthier, safer, more efficient, and better informed now than at any other time in human history.

One might think, in an era where technology abounds, that food-safety testing and analysis techniques have kept pace. Ideally, one might imagine a complex futuristic laboratory, a technological marvel equipped with the latest instrumentation where the precise chemical and bacterial profiles, and their effect on the human body are precisely mapped. In this instance, one would be wrong.

That’s not to say that food-safety laboratories are backward. Their processes are well documented, scientifically sound, and continually improved. Of course, on some level it is sensible to avoid frequently swapping analytical techniques. New methods are a proverbial “dime-a-dozen” and few hold up to their initial promise. When lives are on the line there is little to be gained by exchanging an old, time-tested, technique that may not be quite as efficient for something less-proven and potentially fraught with error.

Still, many believe certain avenues of food-safety could benefit with a bit of modernization. For example, most toxicological studies still utilize an animal model to estimate the risk posed by new chemical substances, and to better understand the way that known pathogenic organisms that effect the body. Animal welfare concerns notwithstanding, a plethora of scientific research has been generated demonstrating the critical flaws in this method. At their best, animal models are poor substitutes for human systems (Mak et al, 2014; Shanks et al, 2009). Put succinctly, there is significant enough deviation between human physiology and that of our closest animal counterparts to make the data from animal testing a poor indicator of the risk to human health and safety.

One might then wonder, how do we ensure that new drugs and food additives are safe? How do we study the downstream effects of dangerous pathogenic bacteria like E. coli, Listeria monocytogenes, and Salmonella enteritidis? The answer, again, may reside in miniaturization. Enter the “Organ-on-a-Chip.”

What is an Organ-on-a-Chip?

The name “Organ-on-a-Chip” seems almost too futuristic. Hearing it, you might imagine a digital reproduction of an organ, existing entirely in silico and tested through the internet. The truth is something even more intriguing and revolutionary.

By combining microfluidics technology (equipment that handles very small volumes of liquid) with advanced cell culture techniques and modern bioengineered materials researchers can create miniature, highly-accurate replicas of human organs.
The essence of the Organ-on-a-Chip is a small glass or plastic rectangular vessel with a maze-like structure of microscopic channels etched into it. These tiny channels contain chemical mixtures, live cells, and various additives that accurately replicate the chemical and biological makeup of human organs. When provided life-sustaining with fluid, applied at a pressure that mimics human blood-pressure, these systems accurately replicate the exact same chemical reactions that are carried out by living human tissue.

In short, the Organ-on-a-Chip behaves just like a real, live human organ, but on a much smaller scale. Treating Organ-on-a-chip systems with potentially toxic new compounds or dangerous bacterial pathogens gives us a better, more-accurate representation of how these factors could harm our own organs, and can help us to avoid and to combat the most dangerous threats.
What makes this organ-on-a-chip so great?

Organ-on-a-Chip technology is still in its infancy, but it is poised to be revolutionary for both food and drug research. Using this new technology, researchers can determine with exceptional precision, precisely how human organs will respond to potential threats (be they bacterial, viral, chemical, or something else entirely).

Circumventing the necessity for animal testing models will keep thousands of laboratory-rats and non-human primates happy, but it also should put a smile on the face of accountants and purchasers. Organ-on-a-chip technology is already surprisingly cost-effective when compared to lifetime costs of maintaining an animal for research.

Combining microfluidics with laboratory robotics holds the promise for accelerating both the pace and reproducibility of critical diagnostic testing. Microfluidics chips are ready-to-use hours after construction; they don’t require weeks or months to mature and grow. They can also be manufactured in a strikingly reproducible manner. Two identical chips will produce identical results every time. By contrast, existing animal-model systems often suffer from reproducibility concerns; even siblings taken from the same litter may produce different results in the same experiment.

Finally, organ-on-a-chip technology offers something critically important that current animal models simply cannot. While change in animals occurs at an evolutionary scale (hundreds of millions of years), we have the ability to actively improve Organ-on-a-Chip technology as we continue to study and refune it. Improved speed, efficiency, and utility will develop as cell culture techniques, microfluidics technology, and laboratory robotics march forward.

Looking to the future: personalized medicine, mass production, and the potential for “you-on-a-chip”

The potential promise delivered by organ-on-a-chip technology is stunning. Researchers have already made great strides in mimicry of certain vital organ functions. Liver and kidney systems have been faithfully reproduced, and inroads made into reproducing the physiological and biochemical profile of other critical systems (heart-, lung-, and artery-on-a-chip are three prominent areas of focus).

Once a sufficient number of systems have been reproduced on microfluidics chips, an obvious path forward is to attempt to join independent systems into an intricate, interconnected framework that is representative of how organs cooperate in the human body. By doing so, it may be possible to test the effect of a dangerous pathogen or a new drug on the entire body. Rather than simply determining how an infection might harm the liver or kidneys, we can observe how it will affect organ systems, or the body as a whole, and how it might disrupt communication and cooperation between different organs and tissues.

Additional hope stems multiplexing organ-on-a-chip technology to get more data from critical research studies. The future of manual labor in the laboratory is in automation and robotics, but working with animals is very difficult to automate because they are varied in size, structure, and behavior. Financial constraints, limited time, and a lack of trained personnel make animal studies cumbersome and difficult to replicate at scale, and have a very small number of replicate samples. In contrast, organ-on-a-chip systems are identical, predictable, and ideal for laboratory automation. A single laboratory robot could power through hundreds of different experiments in a day, collecting substantial quantities of life-saving data.

Finally, some of the largest promise comes from the sphere of “personalized medicine”. For generations, pharmacologists and clinicians have struggled with reproducibility in a clinical setting. A drug or additive given to two different patients may have dramatically different results, and the downstream effects of life-threatening infections are notoriously difficult to predict (some patients recover quickly, while others suffer debilitating long-term effects). Harnessing powerful new genetic and proteomic techniques, researchers may be able to “personalize” organ-on-a-chip technology, generating chips that represent not just generic organ function, but personal organ function. The potential may exist in the future to replicate your organ function, identify your risk factors, and tailor specific treatments just for you.

Building the future of food-safety

Organ-on-a-chip technology has substantial promise in nearly every avenue of medical research and diagnostic testing. With regards to the food-safety, the FDA considers organ-on-a-chip technology sufficiently advanced to merit investment, and they have recently announced a partnership with several private firms to help develop “Liver-on-a-Chip” tech for early stage analysis of food safety concerns.

The dream of the “food-safety laboratory of the future” may still be years or decades away, but with this new technology we can all look forward to the promise of an efficient, optimized, and personalized future for next-generation food-safety.

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