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.

Northeastern professor Shashi Murthy positions a microfluidic device on a microscope stage to prepare for an experiment. Northeastern University photo

North­eastern pro­fessor Shashi Murthy posi­tions a microflu­idic device on a micro­scope stage to pre­pare for an exper­i­ment. North­eastern Uni­ver­sity photo

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.