Researchers at the University of Maryland are using a $2 million grant from the National Science Foundation to develop a “toolbox” that will allow researchers to create their own microfluidic devices for measuring the effects of compounds on nucleic acids, proteins, or cells.
The device, which would enable researchers to input both the compounds to be tested and specific human biological components such as proteins or cells, could significantly improve the speed and accuracy of drug development, according to the university. In line with that goal, the research team is working with three pharmaceutical companies on the development of the device to ensure that it meets the industry’s needs.
William Bentley, chair of the department of bioengineering at UM and principal investigator on the project, told CBA News this week that the work builds on a four-year, $1 million grant his team was awarded by the R.W. Deutsch Foundation last year, “although it goes in a new direction.”
The grant will be used to assemble a team that hails from a variety of disciplines, including bioengineering and biotechnology. Bentley added that UM started a bioengineering graduate program about four years ago, and the interdisciplinary nature of the project allows his team to bring in students from that program.
Bentley said that the Deutsch grant funded a project to develop a nanoscale platform for screening antimicrobials by building a biosynthetic pathway on a chip. “Quorum sensing,” or the communication among bacteria in order to start an infection, was the specific target.
Bentley said that the new funding will allow the team to incorporate cells into the chip and will also enable “multimodal” sensing, or measuring the response to the test compound in the cell using an optical method, an electrical method, and a mechanical method at the same time in the same cell, which provides cross-validation of the parameters being measured.
Another goal of the NSF-funded project is to build ways to “biofunctionalize” devices with biological components after the microfabricated device is constructed, Bentley said, noting that the team is essentially trying to develop a toolbox that allows researchers to put nucleic acids, proteins, or cells onto site-specific registries within patterned microfabricated surfaces on the device.
Co-principal investigators on the project are Greg Payne, director of UMBI's Center for Biosystems Research; Reza Ghodssi, an associate professor with the electrical and computer engineering department of UM’s school of engineering and Institute for Systems Research; and Gary Rubloff, a UM professor with a joint appointment in the engineering school's materials science and engineering department and ISR and director of the Maryland NanoCenter.
Bentley said that the project brings together researchers with microfabrication expertise, molecular biology expertise, polymer processing expertise, and materiology analysis expertise. It is difficult to bring those diverse types of expertise together on the same team, he said.
He said that the project draws heavily from advances in the microfabrication industry, where feature size has almost reached the nanometer level.
“We have been trying to build systems that recruit nature’s capabilities of recognition and assembly, and enhance further those abilities with microfabrication,” Bentley said.
One challenge, Bentley noted, is adding delicate biological components to the chip without damaging them. Currently, the team is using the biopolymer chitosan to address this hurdle.
“Chitosan can actually be electrodeposited onto a surface with the resolution of a microfabricated device, and it forms the scaffold onto which one can bring cells, proteins, and nucleic acids,” he said.
Chitosan is derived from chitin, which is the second most abundant natural biopolymer, said Bentley.
Ultimately, the team envisions the device being able to wirelessly communicate results to another location, said Greg Payne, director of UMBI’s Center for Biosystems Research.
“We have been trying to build systems that recruit nature’s capabilities of recognition and assembly, and further enhance those abilities with microfabrication.”
The researchers are co-developing the device working with researchers from Sanofi-Pasteur, MedImmune, and Bristol-Myers Squibb. These partners “are interested in providing an industry perspective that one normally does not have access to in the university setting,” said Bentley.
Tsu-shun Lee, a deputy director and principal scientist for US manufacturing technology at Sanofi-Pasteur, was one of those who reviewed Bentley’s initial project proposal. The representatives from pharma will meet with Bentley and his team in the future to share information and ideas, Lee said.
“I hope this device can give me more direct measurements of the cell’s physiological condition, compared to today’s indirect measurements,” Lee said. “This will help me to make better decisions about the drug development process and may play an important role in monitoring the production process.”
Bentley said that current cell-based assays currently do not capture the complexity of human biology. “We are developing a device that would allow researchers to test biological systems, including human systems, where the system is pretty faithfully reproduced onto a device,” Bentley said.
He added that such a system on such a device could eventually replace the plate-based screening methods that are the norm in pharma today.
Miniaturization of Drug Discovery
There is rising demand in the drug discovery market for microfluidic devices on which in vivo systems have been recreated, said Michael Shuler, chair of the biomedical engineering department and a professor of biomedical engineering and chemical engineering at Cornell University.
Shuler and his team have developed a similar technology called ”animal-on-a-chip,” which they recently licensed to the Hurel Corporation.
Shuler said that many researchers are interested in in vitro systems to reduce their dependency on animal testing — for practical, ethical, and financial reasons. Such models, in combination with selective in vivo tests, can be much more predictive than animal models in terms of the human response to drugs, he said.
“This predictive ability will give researchers much greater success in human trials. That will, I believe, drive the demand for these devices,” he said.