Northeastern professor of chemical engineering Shashi Murthy has received a four-year, $1.4 million award from the National Institutes of Health to develop a novel instrument that would automate an important process used in creating effective vaccines.

Murthy’s research focuses on designing microfluidic devices for applications in clinical diagnostics and medicine. He explained that this proposed new microfluidic instrument would essentially take in a blood sample and turn one type of cell, monocytes, into another type—dendritic cells.

“This will make it much easier for researchers doing vaccine development to do their work,” Murthy said.

Dendritic cells are a type of antigen-presenting cell that are present in the blood and elsewhere in the body, and Murthy said they are an indispensable part of our protective immunities against pathogens and injury. These cells have been described as “the conductors of the orchestra.” They sense when an infection has entered the body and send instructions to the T cells on how to respond. T cells are white blood cells and play a front-line role in the body’s immune system.

The context of vaccinations
A vaccine works by providing dendritic cells with information on a particular type of infection. This allows the dendritic cells to “know what to do” (i.e. send instructions to T cells) when such an infection is encountered in the future.  According to Murthy, scientists need lots of dendritic cells to test vaccine candidates. The problem is that the body doesn’t create many dendritic cells and they can’t be readily multiplied outside the body.

There is another way, though. Monocytes can be turned into dendritic cells, and scientists have been doing this for years, Murthy said. However, it’s a painstaking manual process that takes about 16 steps and requires significant personnel hours even when modestly scaled up for tens of samples to study only one or two conditions.

Murthy is seeking to ease what he calls a “tremendous bottleneck” by developing a fully-automated microfluidic system that takes in a blood sample and generates these dendritic cells.

The current manual process also takes about six days, and Murthy believes the instrument he’s developing will significantly reduce that timeframe. This project will put his hypothesis to the test.

Personalized medicine
Murthy said that dendritic cells are also key elements of the emerging field of personalized vaccines. He noted the growing interest in developing personalized vaccine-based therapies for diseases like cancer. To accomplish this means examining how the cells of an individual person will react to a particular vaccine, or if there are individuals who can be identified for treatment with a specific vaccine.

He said that instead of just having simply an adequate supply of dendritic cells from an overall population, his system would help do this in a personalized manner.

“The proposed system plays a role in that, too,” he said, “By making it easier to get dendritic cells, it would allow an immunologist to focus more time on designing new vaccine candidates and assessing their efficacy.”

An important collaboration
In this project Murthy will collaborate with physician scientist Daniel Hoft, director of the Division of Infectious Diseases, Allergy & Immunology at the Saint Louis University School of Medicine. Hoft is an internationally known expert in immunology and infectious diseases and the goal of his work is to develop new vaccines that protect against mucosally-transmitted, intracellular pathogens.

This four-year effort will include substantial scientific and programmatic involvement of the National Institute of Allergy and Infectious Diseases and will result in an instrument that can be broadly deployed. In this respect, Murthy’s prior experience in translating laboratory discoveries to commercialized products will play a valuable role. Murthy serves as the founding director of the Michael J. and Ann Sherman Center for Engineering Entrepreneurship Education at Northeastern, and he co-founded Quad Technologies, a company focused on developing novel cell purification tools, based on work on a prior NIH-funded project. Quad has received support from IDEA, Northeastern’s student-run venture accelerator.

“The proposed project is an outstanding example of the high-impact research happening in the college, and our ongoing commitment to creating and translating knowledge for societal impact,” said Nadine Aubry, dean of Northeastern’s College of Engineering. “With their combined expertise in vaccinology, microfluidics, and device commercialization, Professor Murthy and his collaborators are absolutely the right team to develop new tools to quickly and safely develop new vaccines—a critical need with tremendous potential to benefit society worldwide.”

The project is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.