Portland, Ore. - Microelectromechanical systems researchers are getting close to a complete "animal-on-chip" that would allow medical experiments now requiring live animals to be run in vitro on microfluidic chips. The new approach to medical research is based on housing every type of cell inside a microfluidic circulatory system, which is fabricated using semiconductor equipment.
In addition to eliminating animals from experimentation, the new devices use commonly available real human cells that are kept alive in culture. The software and circuitry on the chip provide the cells with the chemicals that enable them to perform as if they were in a living body and built-in sensors constantly monitor cell response in real-time.
"We believe the animal-on-chip is not only more ethically palatable than using lab animals, but it will also be more accurate because of its built-in sensors and because we will be using real human cells in our tests," said assistant professor Shuichi Takayama at the University of Michigan (Ann Arbor), whose lab has developed an animal-on-chip.
"Several labs are now working with animals-on-chip, because it makes so much sense to integrate the sensors into the chip along with the microfluidics to nurture the cells," Takayama said.
In a full-blown animal-on-chip, according to Takayama's vision, each type of living cell-muscle, bone, lung, brain, liver, kidney-would be interconnected by a heartlike circulatory system that would simulate the metabolism of a human. However, the biological system would have built-in sensors to monitor its tiniest reactions, enabling the animal-on-chip to sense toxins before they reach dangerous levels. As a diagnostic tool, the system could perform tests on fluids from sick patients. For example, a patient could be asked to cough into a calculator-like device that then would measure the reactions of the on-chip cells and read out the malady.
Animals-on-chip were first popularized by Cornell University chemical engineers at professor Michael Shuler's lab.
Although many laboratories are working on microfluidic pumps, valves and even complete organ subsystems, devices that can be integrated onto a microfluidic chip and be remotely controlled by a computer are rare. To remedy that, Takayama came up with the idea, and suggested it to one of his students, Wei Gu, that Braille haptic displays might be enlisted as actuators. Takayama reasoned that the pins that help the blind feel raised dots representing letters could be repurposed to pinch on and off tiny microfluidic channels. Theoretically, by writing software to sequence the raising and lowering of the Braille display's pins, all the complex metabolic mechanisms for exchanging fluids among cells could be simulated.
"The overall idea is that by writing software to control the flow of fluids around a chip that has different types of cells, we can re-create the environment in different parts of the body, but in a single culture," said Gu.
Gu's success earned the college senior a $15,000 award for first place in the Collegiate Inventor's Competition last month. Takayama received $5,000. The competition is a program of the U.S. Patent and Trademark Office's National Inventors Hall of Fame.
The cells of the current prototype chip can only be kept alive and healthy for about four weeks, but in future versions, Gu envisions devices that could be seeded with undifferentiated stem cells-the tabula rasa, or clean slate, of biology. Then, by sequencing the correct combinations of hormones and nutrients into separate compartments on the chip, the cells could be differentiated into all the various types that make up a real body, but in a miniature organism that could be kept alive indefinitely. By controlling its metabolism, again by sequencing the Braille display's pins, many types of biological sensors and experiments could be performed.