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Clinical Laboratories and Pathology Groups

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MIT Engineers Develop Physiome-on-a-Chip Device That Tests Multiple Human Organs for Drug Effects; Could it Become a New Clinical Laboratory Test for Complex Multi-Analytes?

“On-a-chip” devices continue to advance and medical laboratories will be natural repositories for patient data as the technology continues to improve

Dark Daily has predicted that the future of clinical laboratory testing will include highly complex multi-analyte test panels. The biomarkers, however, could number in the hundreds or thousands. So, it’s interesting to see new research by a Massachusetts Institute of Technology (MIT) team currently developing a multi-biomarker organ test device for clinical purposes.

Motivated by the costly failure of animal testing efforts to develop drug safety and efficacy in humans, the MIT research engineers created a microfluidic platform technology they dubbed “physiome-on-a-chip,” or more colloquially, “body-on-a-chip.” Their goal is to identify drug reaction in different cell groups within the body (in vivo).

They acknowledged contributions of in vitro microphysiological systems (MPSs), AKA “organ-on-a-chip” (OOC) systems. They note, however, in their paper published in Scientific Reports, that more complex systems that interconnect and receive data from multiple MPSs are needed due to increasing limitations arising from drugs’ “lack of efficacy” rather than toxicity.

“Here we describe the development and implementation of multi-MPS platforms, AKA physiome-on-a-chip, supporting four-way, seven-way, and 10-way MPS interactions for several weeks,” the MIT engineers wrote.

Though MIT’s new technology needs further research and development time, as well as clinical trials, this type of chip design and its ability to scale is a positive development and progress toward Dark Daily’s prediction. Once finalized, it could be adopted in medical laboratories for many types of diagnostic testing purposes.

Researchers Motivated to Improve Drug Efficacy

According to an MIT news release, “MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body.”

The “body-on-a-chip” technology, MIT says, is aimed at determining how drugs may affect one organ while also having side effects on others.

“Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic. With our chip, you can distribute a drug and then look for the effects on other tissues and measure the exposure and how it is metabolized,” said Linda Griffith, PhD, Professor of Teaching Innovation at MIT’s School of Engineering, and a senior author of the study, in the news release.

According to MIT, factors affecting the effectiveness of pharmaceuticals may include:

  • Genetics;
  • Environment;
  • Personal lifestyles; and,
  • Interactions with other drugs.

TechCrunch called the study “unprecedented,” pointing to the platform’s connection of so many tissues and the technology’s ability to keep them stable for weeks.

“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations,” Linda Griffith, PhD, MIT Professor, MIT School of Engineering, told Science Daily. “I think the field is going to go through a transition where we start to get more information out of a three-organ or four-organ system, and it will start to become cost-competitive because the information you’re getting is so much more valuable.” (Photo copyright: MacArthur Foundation.)

How “Body-on-a-Chip” Works

“Body-on-a-chip” is about the size of a tablet computer and links 10 organ types, including: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle.

Using microfluidic platform technology, the researchers placed one- to two-million cells from human tissue samples into the device and then pushed fluid through the chip to resemble blood flow, the Daily Mail reported, adding that MIT’s MPS platform design features:

  • Compartments made from a plastic block;
  • Passages for fluid to move (as a circulatory system does) between the compartments;
  • A water reservoir to limit fluid evaporation; and,
  • Ability to monitor flow of molecular exchanges and drug distribution.

Essentially, using the MIT device, a drug can be introduced to one organ, processed normally, and then passed to other organs for processing and use in other ways, TechCrunch summarized.

The physiome-on-a-chip system (above schematic) comprises bioengineered devices that nurture many interconnected 3D MPSs representing specified functional behaviors of each organ of interest, designed to capture essential features of in vivo physiology based on quantitative systems models tailored for individual applications such as drug fate or disease modeling. This technology could eventually be utilized for clinical laboratory and anatomic pathology testing. (Image and caption copyright: Victor O. Leshyk/Scientific Reports.)

Drug Delivery, Effects on Multiple Tissues Noted in MIT Study

The MIT researcher engineers reported these findings and accomplishments:

  • Delivering a drug to the gastrointestinal tissue;
  • Replicating digesting a drug;
  • Observing as a drug was transported to other tissues and metabolized;
  • Measuring a drug’s path; and,
  • Noting effects of a drug on different tissues and how drugs break down.

“The huge potential of MPS technology is revealed by connecting multiple organ chips in an integrated system for in vitro pharmacology. This study beautifully illustrates that multi-MPS ‘physiome-on-a-chip’ approaches, which combine the genetic background of human cells with physiologically relevant tissue-to-media volumes, allow accurate prediction of drug pharmacokinetics and drug absorption, distribution, metabolism, and excretion,” said Kevin Healy, PhD, Professor of Bioengineering and Materials Science and Engineering, at University of California Berkeley in the MIT news release. Healy was not involved in the research.

Unique Device Design

In addition to making it possible to study so many different tissue types, the device design, according to MIT, is unique for these reasons:

  • Its open microfluidic system, rather than a closed system, means the lid can be removed to manipulate tissue samples;
  • Instead of external pumps common in closed systems, the MIT team used “on-board pumps” to control flow of liquid between the organs; and,
  • The pumps used enabled larger engineered tissues, such as those from tumors in an organ, to be assessed.

The MIT engineers next plan to focus on specific organs—including the brain, liver, and gastrointestinal tissue—to model Parkinson’s disease, Digital Trends reported.

As healthcare providers and medical laboratories adopt precision medicine, MIT’s contributions are both timely and important. The ability to accommodate many different configurations in one platform is impressive, and something Dark Daily has been anticipating.

—Donna Marie Pocius

Related Information:

A “Body-on-a-Chip” Strings Together 10 Model Human Organs

“Body-on-a-Chip” Could Improve Drug Evaluation

MIT Builds “Body-on-a-Chip” Device That Can Store up to 10 Artificial Organs at Once

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies

MIT Gadget Puts Multiple Artificial Organs into a Paperback-Sized Connected System

Drug Testing Could Get a Boost from MIT’s “Body-on-a-Chip”