Scientists at Los Alamos National Laboratory, Los Alamos, NM, working in conjunction with researchers at Vanderbilt University, Nashville, TN, and others, have created ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer. They say that this project, which is focused on creating surrogate human organs, coupled with input from highly sensitive mass spectrometry technologies, could revolutionize the way drugs and toxic agents are screened.

Fig. 1 – The ATHENA organ project combines heart, liver, kidney, and lung features in a desktop toxicity testing platform.

The ATHENA team, is developing four human organ constructs—liver, heart, lung, and kidney—that are based on a significantly miniaturized platform. Each organ component will be about the size of a smartphone screen, and the whole ATHENA “body” of interconnected organs could fit neatly on a desk.

“By developing this ‘homo minutus,’ we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs,” said Rashi Iyer, a senior scientist at Los Alamos National Laboratory, the lead laboratory on the five-year, $19 million multi-institutional effort.

“By creating a holistic dynamic system that more realistically mimics the human physiological environment than static human cells in a dish, we can understand chemical effects on human organs as never before,” Iyer said. “The ultimate goal is to build a lung that breathes, a heart that pumps, a liver that metabolizes and a kidney that excretes, all connected by a tubing infrastructure much akin to the way blood vessels connect our organs.”

Ultimately, the project’s goal is to connect the individual organ modules chemically in a fashion that mimics the way the organs are connected in the body, via a blood surrogate. Devices of this type could also be extremely useful in the field of toxicology. Of the tens of thousands of chemical compounds being used routinely in commerce today, only a small fraction has been tested for toxicity. And even those have been examined only for acute toxicity, not for sublethal or chronic effects, because of the expense and time required by such tests. Human organ construct/ organ-on-a-chip technology could make this process substantially cheaper and faster, they say.

In addition to Vanderbilt and Los Alamos, the ATHENA project combines efforts from top research organizations, including the Berlin-Brandenburg Center for Re gen erative Therapies, Charite Universitätsmedizin, Berlin; Harvard University, Cambridge, MA; University of California, San Francisco; and CFD Research Corporation, Huntsville, AL.

Charite’s original organ perfusion system cost $80,000 and was the size of a small refrigerator. Using simple microfluidics, the team was able to create a 5 × 4 × 3.5-inch perfusion device that costs about $2,000 to make, they reported. They have validated its basic characteristics and demonstrated that it can keep human liver cells healthy for an extended period of time.

In addition to successfully shrinking the organ platform, Vanderbilt re searchers connected the organ platform to a powerful ion mobility-mass spectrometer, which can simultaneously detect and identify minute quantities of thousands to tens of thousands of different biological molecules simultaneously. The team plans on hooking up their liver device to the Harvard heart this winter. They expect to add the lung construct being developed at Los Alamos next year and the UCSF/Vanderbilt kidney the year after.