Vanderbilt-led team to develop ‘microbrain’ to improve drug testing


Take a millionth of a human brain and squeeze it into a special chamber the size of a mustard seed.

Link it to a second chamber filled with cerebral spinal fluid and thread both of them with artificial blood vessels in order to create a microenvironment that makes the neurons and other brain cells behave as ifthey were in a living brain.

Then surround the chambers with a battery of sensors that monitor how the cells respond when exposed to minute quantities of dietary toxins, disease organisms or new drugs under development.

Creating such a “microbrain bioreactor” is the challenge of a new $2.1 million research grant awarded to an interdisciplinary team of researchers from Vanderbilt University, Vanderbilt University Medical Center, the Cleveland Clinic and Meharry Medical College.

John Wikswo


John Wikswo, the Gordon A. Cain University Professor and director of the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE), is orchestrating the multidisciplinary effort. Wikswo also is a professor of biomedical engineering.

The grant is one of 17 that are being issued by the National Center for Advancing Translational Sciences at the National Institutes of Health as part of a $70 million “Tissue Chip for Drug Testing” program. The five-year program is a cooperative effort on the part of NIH, the Defense Advanced Research Projects Agency and the FDA.

The brain is a particularly difficult target for drug development because it is surrounded by three barriers that protect it from molecular or cellular intruders. The most formidable of these is the blood-brain barrier (BBB). It surrounds the blood vessels that service the brain and allows the passage of compounds that the brain needs while simultaneously blocking the passage of other types of molecules, both foreign and domestic. The two other barriers protect the neurons from contaminants in the cerebral spinal fluid and protect the cerebral spinal fluid from contaminants in the blood. Not only do these barriers block potentially harmful molecules, neuroscientists have also discovered that they occasionally alter the chemistry of some of the compounds that they let through.

The basic microbrain bioreactor involves the integration of several technologies that have been developed and tested independently.

A team headed by Deyu Li, associate professor of mechanical engineering, and Donna Webb, assistant professor of biological sciences, will incorporate special microfluidic valves that they developed to study the interactions between neurons and the glial cells that accompany them in the brain.

These simple valves allow the scientists to maintain different types of cells in individual chambers linked by microchannels that can be easily opened and closed. This capability allowed Webb’s team to show that fluid from the glial cells is critical for neuron survival. “The new platform, with its unprecedented complexity, will greatly advance the lab-on-a-chip field,” Li said.

Read more about other technologies here. (